Skin nontumor

Dermal perivascular and vasculopathic reaction patterns

Cutaneous vasculitis


Editorial Board Member: Jonathan D. Ho, M.B.B.S., D.Sc.
Mariel Molina Nunez, M.D.
Jose A. Plaza, M.D.

Last author update: 7 March 2023
Last staff update: 12 February 2024

Copyright: 2002-2024, PathologyOutlines.com, Inc.

PubMed Search: Cutaneous vasculitis

Mariel Molina Nunez, M.D.
Jose A. Plaza, M.D.
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Cite this page: Molina Nunez M, Plaza JA. Cutaneous vasculitis. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/skinnontumorvasculitis.html. Accessed April 14th, 2024.
Definition / general
  • Vasculitides are inflammatory processes that can affect capillaries, venules and small, medium and large sized vessels (Curr Opin Rheumatol 2019;31:46, An Bras Dermatol 2020;95:355)
  • Cutaneous vasculitis can present in several forms: a component of systemic vasculitides, a limited expression of systemic vasculitis or a single organ vasculitis (Arthritis Rheumatol 2018;70:171)
  • Many classifications have been proposed; however, the most accepted one is the Chapel Hill consensus conference which integrates the clinical presentation, histopathology and lab findings; it also classifies vasculitis based on the size of the affected vessel in small, medium and large vessel vasculitis (Arthritis Rheum 2013;65:1)
Essential features
  • Vasculitis represents inflammation of the capillaries, postcapillary venules and small, medium and large sized vessels
  • Variable clinical presentation (purpura, erythema, papules, ulcer, etc.)
  • Majority of cutaneous vasculitides are self limited and have an excellent prognosis
  • Etiology of cutaneous vasculitis is multifactorial but generally presents as a result of an immune hypersensitivity reaction, associated with direct damage of the vessel wall and inflammation
  • Clinical presentation, skin biopsy and direct immunofluorescence are crucial to establish a definitive diagnosis
  • Treatment varies depending on the nature of the disease and includes symptomatic treatment (self limited conditions), steroids or immunomodulators
Terminology
  • Vasculitides
ICD coding
  • ICD-10:
    • D89.1 - cryoglobulinemia
    • L95 - vasculitis limited to skin, not elsewhere classified
    • L95.1 - erythema elevatum diutinum
    • M30.1 - polyarteritis with lung involvement (Churg-Strauss)
    • M31.7 - microscopic polyangiitis
    • M31.9 - necrotizing vasculopathy, unspecified
    • M35.2 - Behçet disease
  • ICD-11:
    • 4A44.A1 - granulomatosis with polyangiitis
Epidemiology
  • Cutaneous vasculitides affect both genders equally and patients of all ages
  • Presence of an underlying systemic vasculitis, connective tissue disease or malignancy is much more common in adults than in children (Mayo Clin Proc 2014;89:1515)
  • Overall annual incidence of cutaneous vasculitis is ~38.6 per million (J Rheumatol 1998;25:920)
Sites
  • Systemic vasculitides can involve cranial or peripheral nerves, gastrointestinal tract, retina, aorta, kidneys, oral mucosa and skin, among other organs (Circulation 2021;143:267)
  • Most types of vasculitis affect the lower extremities (Pathologe 2020;41:355)
Pathophysiology / etiology
  • Small vessel vasculitis:
  • Medium vessel vasculitis:
  • Large vessel vasculitis:
    • Giant cell arteritis:
    • Takayasu arteritis:
      • Unknown pathogenesis; is thought to be a combination of immune mediated process and genetic predisposition
      • Granulomatous inflammation of the media and adventitia (Heart 2018;104:558)
    • Behçet disease:
      • Affects arteries and veins
      • Recurrent oral or genital aphthous ulcers accompanied by cutaneous, ocular, articular, gastrointestinal or central nervous system inflammatory lesions
      • Leukocytoclastic vasculitis of small vessels affecting mostly venules
    • Cogan syndrome:
      • Arteritis and aortitis
      • May present with aortic aneurysm or mitral valvulitis
      • Vasculitis of small arteries in the panniculus and dermosubcutaneous junction
    • Vasculitis associated with systemic diseases (systemic lupus erythematosus, rheumatoid arthritis, sarcoidosis):
      • Vasculitis of small or medium sized vessels
      • Presents as a component of the systemic condition
      • Present with cutaneous leukocytoclastic vasculitis
    • Vasculitis associated with probable etiology:
      • Caused by drugs, infections (sepsis) or autoimmune conditions such as Sjögren syndrome
      • Present with cutaneous leukocytoclastic vasculitis
    • Nodular vasculitis:
      • Vasculitis with lobular panniculitis of mostly postcapillary venules
    • Erythema elevatum diutinum:
      • Neutrophilic dermatosis with chronic localized fibrosing leukocytoclastic vasculitis
    • Granuloma faciale:
      • Chronic, progressive, inflammatory dermatosis
      • Characterized by asymptomatic papules, nodules or plaques of red-brown to violaceous color
      • Perivascular inflammatory infiltrates in the dermis with leukocytoclasis
      • Necrotizing vasculitis is rare (StatPearls: Granuloma Faciale [Accessed 31 January 2023])
    • Palisaded neutrophilic and granulomatous dermatitis:
    • Hypergammaglobulinemic purpura of Waldenström:
Clinical features
  • Skin is the most frequently involved organ in vasculitides and is usually the first organ to reveal signs of systemic disease; skin involvement by vasculitides may lead to significant morbidity and mortality (Z Rheumatol 2013;72:436, Curr Opin Rheumatol 2022;34:25)
  • Small vessel vasculitis:
    • Cutaneous leukocytoclastic vasculitis:
      • Presents as petechiae, confluent purpura, urticarial hives or deep ulcers and nodules
      • Mainly affects the lower extremities and back (Intern Emerg Med 2021;16:831)
    • Immunoglobulin A vasculitis (Henoch-Schönlein purpura):
    • Cryoglobulinemic vasculitis:
      • Most patients are asymptomatic
      • Symptomatic patients present with ulcers, gangrene, urticaria, livedo reticularis, purpura, retinal hemorrhages and neurologic disturbances (J Autoimmun 2019;105:102313)
    • Hypocomplementemic urticarial vasculitis (anti-C1q vasculitis):
      • Leukocytoclastic vasculitis, severe angioedema, laryngeal edema, pulmonary involvement, arthritis, arthralgia, glomerulonephritis and uveitis (Curr Rheumatol Rep 2009;11:410)
    • Antineutrophil cytoplasmic antibody (ANCA) associated vasculitis:
      • Rhinosinusitis, arthralgia, dyspnea, cough, hemoptysis, purpura, renal involvement, neurologic dysfunction (Eur J Intern Med 2020;74:18)
    • Microscopic polyangiitis:
    • Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome):
      • Constitutional symptoms, maxillary sinusitis, asthma, arthritis, peripheral neuropathy, focal or crescentic glomerulonephritis (less frequent), purpura mainly in lower extremities (Semin Respir Crit Care Med 2018;39:471)
    • Granulomatosis with polyangiitis (Wegener granulomatosis):
  • Medium vessel vasculitis:
    • Polyarteritis nodosa:
      • Constitutional symptoms, myalgia, arthralgia, gastrointestinal and skin involvement (Curr Opin Pediatr 2022;34:229)
      • Cutaneous polyarteritis nodosa is a variant of polyarteritis nodosa confined to the skin, muscle and peripheral nerves in the absence of systemic involvement (Clin Exp Dermatol 1983;8:47)
    • Kawasaki disease:
      • Oral mucosa erythema and cracked lips, strawberry tongue, conjunctivitis, polymorphous rash, extremity changes, lymphadenopathy (Curr Rheumatol Rep 2020;22:75)
  • Large vessel vasculitis:
    • Giant cell arteritis:
      • New onset headaches, scalp tenderness, jaw claudication, fever, fatigue, polymyalgia and vision loss (Neurol Clin 2019;37:335)
    • Takayasu arteritis:
      • Arterial stenosis, aneurysms and occlusion involving the ascending and descending aorta, renovascular hypertension, lower extremity claudication, arthralgia, myalgia and skin nodules (Heart 2018;104:558, Dermatologica 1990;181:266)
    • Behçet disease:
      • Recurrent aphthous stomatitis, genital aphthous ulcers, erythema nodosum-like lesions, papulopustular lesions, ocular manifestations, thrombophlebitis, pericarditis, myocarditis, arthralgia, fibromyalgia, neurologic and gastrointestinal manifestations (Clin Dermatol 2017;35:421)
    • Cogan syndrome:
    • Vasculitis in systemic lupus erythematosus:
      • Petechiae, palpable purpura, papulonodular lesions, livedo reticularis and ulcers are associated with myocarditis, serositis and Raynaud phenomenon (Clin Dermatol 2004;22:148)
    • Rheumatoid arthritis associated vasculitis:
      • Purpura, ulcers, gangrene, mononeuritis multiplex, episcleritis, scleritis, myocarditis, pericarditis, lung, kidney, gastrointestinal and central nervous system involvement (Curr Opin Rheumatol 2015;27:63)
    • Sarcoid vasculitis:
      • Constitutional symptoms, peripheral adenopathy, rash, scleritis, iridocyclitis, musculoskeletal and pulmonary parenchymal involvement (Semin Arthritis Rheum 2000;30:33)
Diagnosis
  • Proper diagnosis requires a combination of clinical history and physical examination to assess organ involvement (systemic disease)
  • Obtain a complete blood count, complete metabolic panel and urinalysis
  • Specific tests depending on the etiology include infectious disease serology (hepatitis C, B, HIV), immunoglobulin levels, C3 and C4 complement levels, antinuclear antibody, rheumatoid factor, antineutrophilic cytoplasmic antibodies, cryoglobulins and anti-CPP, amongst others
  • Skin biopsy remains the cardinal step in confirming diagnosis of cutaneous vasculitis; direct immunofluorescence contributes to an accurate diagnosis and differentiates it from pseudovasculitic disorders (Am J Clin Pathol 2005;124:S84, Am J Dermatopathol 2005;27:504, Curr Opin Rheumatol 2022;34:25, Am J Clin Dermatol 2008;9:71)
  • In cases of systemic vasculitis, a kidney or nerve biopsy can provide additional diagnostic elements
  • Complementary laboratory exams, including workup for infectious, autoimmune disorders or malignancy, may be needed (An Bras Dermatol 2020;95:355)
Laboratory
Prognostic factors
Case reports
  • 4 year old boy presented with pruritic, nonblanching maculopapular rash in association with COVID-19 infection (BMJ Case Rep 2021;14:e239910)
  • 7 year old sisters presented sequentially with erythematous nodules in trunk and lower extremities associated with pain (Mod Rheumatol 2018;28:1049)
  • 16 year old girl presented with fever, myalgia, diarrhea and an erythematous maculopapular rash in abdomen and arms (BMC Gastroenterol 2020;20:352)
  • 17 year old girl without significant past medical history presented with arthralgia, facial and lower extremity edema (Lupus 2014;23:1426)
  • 78 year old women presented with recalcitrant skin ulcer in her right ankle (J Dermatol 2018;45:1009)
Treatment
Clinical images

Contributed by Jose A. Plaza, M.D.

Polyarteritis arteritis nodosa

Leukocytoclastic vasculitis

Urticarial vasculitis

Microscopic (histologic) description
  • Cutaneous vasculitis:
    • Small vessel cutaneous vasculitis affects arterioles, capillaries and postcapillary venules in the superficial and mid dermis
    • Medium vessel cutaneous vasculitis involves small arteries and veins within the deep dermis and subcutis
    • Timing and proper sampling is key to yield a definitive diagnosis
    • Ideally, a skin biopsy should be made within 24 - 48 hours of appearance
    • Classic histopathologic feature is leukocytoclastic vasculitis:
      • Swelling of the vessel wall (primarily postcapillary venules)
      • Transmural infiltration of neutrophils
      • Degranulation and fragmentation of neutrophils creating nuclear dust
      • Fibrinoid necrosis and extravasation of red blood cells
      • Signs of endothelial damage
      • When lesions have more than 48 - 72 hours are predominantly infiltrated by mononuclear cells instead of neutrophils (Bolognia: Dermatology, 4th Edition, 2017)
  • Small vessel vasculitis:
    • Cutaneous leukocytoclastic vasculitis:
      • Fibrinoid necrosis / intraluminal fibrin deposition
      • Disruption of the vessel wall with red cell extravasation
      • Leukocytoclasia or nuclear dust
      • Eccrine gland necrosis
      • Granulomas may or may not be present depending on the underlying entity (J Autoimmun 2022;127:102783)
      • Direct immunofluorescencecan show deposits of IgM, IgG, IgA and C3 along the dermoepidermal junction and the superficial vasculature (Clin Dermatol 2022;40:639)
    • IgM / IgG vasculitis:
      • Leukocytoclastic vasculitis with IgM / IgG deposition
    • IgA vasculitis (Henoch-Schönlein purpura):
      • Leukocytoclasia and IgA deposition
    • Cryoglobulinemic vasculitis:
      • Leukocytoclastic vasculitis, vessels obstruction and ischemia (type I)
      • Mixed cryoglobulinemia (type II and III) is due to immunocomplex deposition
      • Cold urticaria, palpable purpura, livedo reticularis and Raynaud phenomenon are part of the cutaneous manifestations
      • Diffuse proliferative glomerulonephritis (J Autoimmun 2019;105:102313)
    • Hypocomplementemic urticarial vasculitis:
      • Leukocytoclasia and anti-C1q antibodies deposition
    • Microscopic polyangiitis:
    • Eosinophilic granulomatosis with polyangiitis:
    • Granulomatosis with polyangiitis:
    • Urticarial vasculitis:
      • Most often affects postcapillary venules in the dermis
      • Leukocytoclastic vasculitis with endothelial swelling, karyorrhexis of neutrophils, fibrin deposition in the vessel wall, luminal occlusion and extravasation of erythrocytes in the dermis (Immunol Allergy Clin North Am 2014;34:141)
      • Perivascular infiltrate comprised mainly of neutrophils, eosinophils or lymphocytes (Int J Womens Dermatol 2021;7:290)
      • Inflammatory infiltrate tends to shift with time, from predominantly neutrophils to primarily lymphocytic (Am J Dermatopathol 2020;42:399)
  • Medium vessel vasculitis:
    • Polyarteritis nodosa (PAN):
    • Kawasaki disease:
      • Acute process is expressed as nongranulomatous, necrotizing arteritis with neutrophilic infiltration
      • Subacute process presents with asynchronous infiltration of lymphocytes, plasma cells and eosinophils
      • Chronic process is comprised of a luminal myofibroblast proliferation associated with chronic inflammation
      • Progressive arterial stenosis (Circulation 2017;135:e927)
  • Large vessel vasculitis:
    • Large vessel vasculitis:
      • Affects the aorta and branches of major vessels
      • Segmental granulomatous involvement with prominent inflammation of the intima and media
      • Fibrosis of the adventitia (Vasc Med 2019;24:79)
    • Giant cell arteritis:
    • Takayasu arteritis:
      • Granulomatous inflammation of the media and adventitia
      • Infiltration of lymphocytes, macrophages, plasma cells and giant cells
      • Fibrosis with scarring leading to stenosis (Heart 2018;104:558)
    • Behçet disease:
      • Fibrinoid necrosis
      • Endothelial swelling
      • Significant neutrophilic and mononuclear infiltration around dermal vessels
      • Mucocutaneous lesions show leukocytoclasia, lymphocytic infiltration, immunoglobulin and complement deposition with subsequent liquefactive degeneration at the at the dermoepidermal junction, ending in ulcer formation (Autoimmun Rev 2018;17:567)
      • Can present with folliculitis or papulopustular lesions associated with vasculitis (An Bras Dermatol 2017;92:452, Yonsei Med J 2007;48:573)
    • Cogan syndrome:
      • Histopathologic examination of cochlear and corneal tissue show lymphocytic and plasma cell infiltration (Autoimmun Rev 2013;12:396)
    • Vasculitis in systemic lupus erythematosus:
    • Rheumatoid arthritis associated vasculitis:
      • Vessel wall necrosis
      • Leukocytoclasia
      • Mononuclear and neutrophilic infiltration of small to medium sized vessels
      • Disruption of the internal and external elastic lamina (Curr Rheumatol Rep 2010;12:414)
    • Sarcoid vasculitis:
      • Well defined noncaseating granulomas
      • Multinucleated giant cells
      • Leukocytoclasia
      • Dermal fibrosis
      • Epidermal changes include a lichenoid / interface inflammatory pattern, apoptotic keratinocytes
      • Asteroid and Schaumann bodies can be present (Australas J Dermatol 2010;51:198)
    • Erythema elevatum diutinum:
      • Early lesions show leukocytoclastic vasculitis in the upper to mid dermis composed by a neutrophilic infiltrate with some eosinophils (Am J Dermatopathol 2005;27:397)
      • Progression of the lesions show involvement of the papillary and periadnexal dermis
      • Mature lesions exhibit granulation tissue, fibrosis, mixed inflammation and intracellular lipoidosis (J Am Acad Dermatol 1993;29:363)
      • Direct immunofluorescence demonstrates IgG, IgM, C3 and fibrinogen deposits in the vessel wall within the upper dermis (J Am Acad Dermatol 1992;26:38)
    • Granuloma faciale:
    • Palisaded neutrophilic and granulomatous dermatitis:
Microscopic (histologic) images

Contributed by Jose A. Plaza, M.D. and Medical College of Wisconsin Dermatology Department

Polyarteritis arteritis nodosa

Urticarial vasculitis

Urticarial vasculitis


Leukocytoclastic vasculitis

Leukocytoclastic vasculitis


Leukocytoclastic
vasculitis
involving vessels
in the papillary

Leukocytoclastic vasculitis

Leukocytoclastic vasculitis

Immunofluorescence description
  • Predominantly IgA1 deposits in the postcapillary venules (Henoch-Schönlein purpura) (Pediatr Dermatol 2008;25:630, Arthritis Rheumatol 2018;70:171)
  • Depending on the age of the lesions, skin biopsies of leukocytoclastic vasculitis can show deposition of IgG, IgA, IgM or complement C3 (Am J Dermatopathol 2006;28:486)
  • Direct immunofluorescence negative cases may reflect sampling error or consumption of immunocomplex
  • Most direct immunofluorescence patterns in leukocytoclastic vasculitis are nonspecific and a negative DIF does not preclude the presence of cutaneous vasculitis (J Cutan Pathol 2018;45:16)
Immunofluorescence images

Contributed by Alexander J. Gallan M.D. and Medical College of Wisconsin Dermatology Department

Glomerulus with mesangial IgA and C3 deposition

Deposits of IgM, IgA and C3



Contributed by Children's Wisconsin Pathology Department

Urticarial vasculitis with deposits of IgA, C3 and fibrin

Sample pathology report
  • Skin, right leg, punch biopsy:
    • Leukocytoclastic vasculitis (see comment)
    • Comment: The specimen shows superficial and deep perivascular inflammation comprised predominantly of neutrophils, with marked cellular debris, extravasation of red blood cells, vessel wall expansion and fibrinoid necrosis.
Differential diagnosis
  • Thrombocytopenic purpura:
  • Pigmented purpuric dermatosis:
    • Multiple petechial hemorrhages expressed as red to purple macules
    • Histopathology shows dilated vessels, hemosiderin deposits, red cell extravasation, perivascular lymphohistiocytic infiltration and reaction patterns that can be lichenoid, spongiotic or granulomatous (J Clin Med 2021;10:2283)
    • No vasculitis is seen
  • Senile purpura:
    • Elderly
    • Macules and patches in sun exposed areas
    • Degeneration of vessel wall and supporting stroma (Ann Dermatol 2019;31:472)
  • Embolism and infections:
  • Drug induced vasospasm:
  • Vascular trauma:
    • Hypothenar hammer syndrome is typical in males (often athletes) and is a consequence of recurrent trauma resulting in an aneurysm or thrombosis of the ulnar artery
    • Angiography confirms the diagnosis
    • Histologically recurrent trauma can cause intimal and media hyperplasia and fibrosis (fibromuscular dysplasia) (J Emerg Med 2019;56:105, Am J Dermatopathol 2007;29:44)
  • Calciphylaxis:
    • Fibrointimal hyperplasia
    • Comorbidities: end stage renal disease
    • Chronic, painful, nonhealing wounds
    • Calcification of small to medium size vessels with intimal hyperplasia (Am J Dermatopathol 2013;35:582)
Board review style question #1
Which of the following is true regarding cutaneous vasculitis?

  1. Both Behçet and Schamberg disease present with fibrinoid necrosis of the vessel wall
  2. Microscopic polyangiitis with renal involvement is expressed as rapidly progressive glomerulonephritis
  3. Most cutaneous vasculitides are chronic and recalcitrant
  4. Only small vessel vasculitis present with mucocutaneous manifestations
Board review style answer #1
B. Microscopic polyangiitis with renal involvement is expressed as rapidly progressive glomerulonephritis. Renal involvement by microscopic polyangiitis is characterized by a necrotizing crescentic glomerulonephritis with few or no deposits on immunofluorescence microscopy (Biomed Res Int 2015;2015:402826).

Comment Here

Reference: Cutaneous vasculitis
Board review style question #2


What type of immune deposits can be identified by direct immunofluorescence in cases of leukocytoclastic vasculitis?

  1. C3 and IgA only
  2. IgE
  3. IgG and C3 only
  4. IgG and IgM only
  5. IgG, IgM, IgA and C3
Board review style answer #2
E. IgG, IgM, IgA and C3. Leukocytoclastic vasculitis can show deposits of IgM, IgG, IgA and C3 by immunofluorescence microscopy.

Comment Here

Reference: Cutaneous vasculitis
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