vasculitides & vaso-occlusive disorders · vasculitides & vaso-occlusive disorders ......

VASCULITIDES &

VASO-OCCLUSIVE

DISORDERS

Broward Health Medical Center

Dermatology Residency Program

Program Director: Carlos Nousari, M.D.

Trevor Batty, D.O., Sasha Chediak, D.O., Jennifer

Conde, D.O., Lisa Diaz, D.O., June Kunaparredy,

D.O., Brandon Nickle, D.O., Pamela Sheridan, D.O.,

Brittany Smirnov, D.O., Miguel Villacorta, D.O.

Disclosure

• We have no financial interests or

relationships to disclose.

CUTANEOUS SMALL-VESSEL VASCULITIS

A. Hypersensitivity Vasculitis/Leukocytoclastic

Vasculitis

B. Henoch-Schonlein Purpura

C. Acute Hemorrhagic Edema of Infancy

D. Urticarial Vasculitis

E. Cryoglobulinemic Vasculitis

F. Erythema Elevatum Diutinum

• All ages & sexes, MC in adults• Etiology: immune complex

deposition• Presentation: palpable purpura,

erythematous papules, urticarial lesions involving dependent areas– Koebner phenomenon– Fever, weight loss, myalgias with

flares

• Pathology:– H&E: LCV, karyorrhexis,

extravasated RBC– DIF: C3, IgM, IgA and/or IgG

granular deposits in vessels

HYPERSENSITIVITY VASCULITIS / CUTANEOUS

LEUKOCYTOCLASTIC VASCULITIS (LCV)

Bolognia, Jean, Joseph L. Jorizzo, and Julie V.

Schaffer. Dermatology. Philadelphia: Elsevier Saunders,

2012. Print.

• Secondary LCV• Idiopathic (50%)• Infection (15-20%)• Inflammatory Disorders (15-20%)• Drug Exposure (10-15%)• Neoplasms (2-5%)• Genetic Disorders (Rare)

• Treatment:– Acute

• Often resolves without treatment• Avoid trigger• Supportive care

– Chronic (>4 wks)• Colchicine, dapsone,

corticosteroids

HYPERSENSITIVITY VASCULITIS / CUTANEOUS

LEUKOCYTOCLASTIC VASCULITIS (LCV)


Schaffer. Dermatology. Philadelphia: Elsevier Saunders,

2012. Print.

• MC children • Etiology: bacterial & viral

infections• Presentation: palpable purpura,

arthralgias, abdominal pain, renal disease

• Pathology:– H&E: LCV– DIF: IgA vasculitis

• Treatment: systemic corticosteroids, immunosuppressants, ACE-I

• Prognosis: monitor for chronic renal insufficiency

HENOCH-SCHONLEIN PURPURA

IGA VASCULITIS

Gaskill, Neil; Guido, Bruce; & Mago, Cynthia. (2016).

Recurrent adult onset Henoch-Schonlein Purpura: a case

report. Dermatology Online Journal, 22(8). doj_32191.

• Children < 2 yrs• Etiology: likely infectious• Presentation: cockade, annular,

purpuric plaques involving the face, ears, distal extremities– No systemic findings

• Pathology:– H&E: LCV

– DIF: IgA vasculitis

• DDx: Child abuse, urticaria, urticarial vasculitis, erythema multiforme

• Treatment: Resolves spontaneously in 1-3 weeks

ACUTE HEMORRHAGIC EDEMA OF CHILDHOOD

Mreish S, Al-Tatari H. Hemorrhagic Lacrimation and

Epistaxis in Acute Hemorrhagic Edema of Infancy

Case Rep Pediatr. 2016;2016:9762185.

• Adults, peak 50s, F>M• Etiology: unknown• Variants:

– Normocomplementemic– Hypocomplementemic

• Associations:– CTD (Sjögren’s, SLE)– Serum sickness– Cryoglobulinemia– Infections (HBV, HCV, EBV, Lyme)– Medications – Hematologic & solid malignancies:

colon & renal cell cancer

URTICARIAL VASCULITIS

James W, Berger T, Elston D. (2011) Andrews’ Diseases of

Skin (11th ed.) Edinburgh, London, New York, Oxford,

Philadelphia, St Louis, Sydney, Toronto, Elsevier Inc.

• Presentation: – Erythematous annular or

targetoid wheals resemble urticaria → progress to purpura with residual hyperpigmentation

– Favor trunk or proximal extremities

– > 24 hours– Recurrent lesions– Painful or burning– Systemic findings: angioedema,

arthralgias, abdominal or chest pain, fever, dyspnea, uveitis, glomerulonephritis & Raynaud’s


Bolognia J, Jorizzo J, Schaffer J. et al. (2009) Dermatology

(3rd ed.) Edinburgh, London, New York, Oxford, Philadelphia,

St Louis, Sydney, Toronto, Elsevier Inc.

3 clinical features distinguish skin lesions of urticarial

vasculitis from true urticaria:

1. Lesions are often painful, rather than pruritic.

2. Lesions >24 hrs and are fixed, rather than migrating.

3. Post-inflammatory purpura or hyperpigmentation.

• Diagnosis: skin biopsy– H&E: < 48 hours in onset

– DIF: < 24 hours in onset

• Pathology: – H&E: LCV + neutrophilic infiltrate

– Hypo DIF: C3 granular pattern in BV & BM

• Treatment: – 1st line: antihistamines, NSAIDs

– Alt: colchicine, hydroxychloroquine, dapsone

– Systemic tx: steroids, azathioprine, mycophenolate mofetil, rituximab

• Prognosis: – Chronic and benign ~ 3 years


Rapini, R. (2012). Practical Dermatopathology (2nd ed.)

Edinburgh, London, New York, Oxford, Philadelphia, St

Louis, Sydney, Toronto, Elsevier Inc.

CRYOGLOBULINEMIC VASCULITIS

• Vasculitis is ONLY seen with types II and III

– Type I can present with vasculopathy

• Small & medium-sized vessels, but preferentially involves

small vessels

• Association with HCV & HBV infections

Bolognia, Jean., et al. eds. Dermatology.

[Philadelphia] :: Elsevier Saunders, 2012. Print.


• Palpable purpura MC

• Other findings: erythematous

papules, ecchymoses, nodules,

urticaria, livedo reticularis,

necrosis, ulcerations, bullae

• Extracutaneous findings:

– Arthralgias/arthritis (70%)

– Peripheral sensory neuropathy (40%)

– GI symptoms or hepatitis (30%)

– Membranoproliferative

glomerulonephritis (25%)

1Berera SR et al. A Rare Case of Hepatitis C-Associated Cryoglobulinemic

Duodenal Vasculitis. ACG Case Reports Journal. 2016;3(4):e134.2 Dalai et al. An Unusual Case of HCV Negative Cryoglobulinemia

Presenting as Symmetrical Peripheral Gangrene. Journal of Clinical and

Diagnostic Research 2016;10(4):18-19.


• Laboratory Evaluation:

– Often falsely negative, need to test multiple times

– Blood samples should be kept at 37C (98.6F) while being transported to

lab

• 70% are RF (+); 20% are ANA (+)

• Low C4 levels - do not correlate with disease activity

• Treatment: treat underlying disease!

– Hep C (+): new antivirals (i.e Harvoni), Ribavirin, Interferon

– Plasma exchange or cyclophosphamide with corticosteroids may be

needed for severe renal or neurological involvement

– Rituximab

Bolognia, Jean., et al. eds. Dermatology. [Philadelphia] ::

Elsevier Saunders, 2012. Print.

ERYTHEMA ELEVATUM DIUTINUM

• Symmetric red-violet to red-

brown papules & plaques

• Persistent lesions that develop

on extensor surfaces/small

joints

– Trunk generally spared

– A/w infections, hematologic,

rheumatologic diseases

• Limited to skin

• Pathology: LCV with fibrinoid

necrosis

• Treatment: typically responds

promptly to Dapsone or

sulfapyridine

Momen, S.E., Jorizzo, J. and Al-Niaimi, F. (2014), Erythema

elevatum diutinum: a review of presentation and treatment. J

Eur Acad Dermatol Venereol, 28: 1594–1602.

doi:10.1111/jdv.12566

MIXED (MEDIUM & SMALL) VESSEL VASCULITIS

A. Connective Tissue Disease Associated (usually

rheumatoid vasculitis)

B. Septic Vasculitis

C. ANCA-Associated

1. Microscopic Polyangiitis

2. Granulomatosis with Polyangiitis

3. Allergic Granulomatosis (Churg-Strauss)

A. Polyarteritis Nodosa (benign & systemic)

MEDIUM-VESSEL VASCULITIS

• Classic PAN (25% cases have skin

findings): palpable purpura, livedo

reticularis, retiform purpura,

“punched-out” ulcers

• Cutaneous PAN (10%): painful

subcutaneous nodules & ulcerations

over the lower extremities, particularly

near malleoli

• Extracutaneous manifestations:

– Fever

– Arthralgias

– Myalgias

– Paresthesias

– Abdominal pain

– Orchitis

– Renovascular hypertension

POLYARTERITIS NODOSA

Matteoda MA, Stefano PC, Bocián M, Katsicas MM, Sala J,

Cervini AB. Cutaneous polyarteritis nodosa. Anais

Brasileiros de Dermatologia. 2015;90(3 Suppl 1):188-190.

doi:10.1590/abd1806-4841.20153856.

POLYARTERITIS NODOSA

• Cutaneous variant has chronic, more

benign course

– Often a/w strep infection in children

• HBV, HCV, infections, inflammatory

diseases, malignancies (hairy cell

leukemia) & medications

• Pathology: Segmental necrotizing

vasculitis in subcutaneous tissue

• Treatment– Classic PAN – systemic corticosteroids

(1 mg/kg/day of prednisone)

– Cutaneous PAN – topical or intralesional

steroids, may need systemic steroids if

progressive or extensive

Morgan, A. J. and Schwartz, R. A. (2010), Cutaneous

polyarteritis nodosa: a comprehensive review. International

Journal of Dermatology, 49: 750–756. doi:10.1111/j.1365-

4632.2010.04522.x

• Rare, late complication in patients with

longstanding, erosive, deforming RA

• High morbidity and mortality

• Risk Factors:

– Smoking, HLA-DRB1/similar epitopes,

uncontrolled RA, high +RF titer and anti-

CCP, PVD

• Presentation:

– Purpura, cutaneous ulcers (upper or lower

ext), rheumatoid nodules, digital infarcts,

nail fold infarcts

– Extracutaneous: severe erosive arthritis,

ocular, cardiovascular, pulmonary, renal,

GI, & CNS findings

• Treatment:

– No established guidelines to help guide

therapy, high-dose glucocorticoids +

cyclophosphamide has shown promising

results

RHEUMATOID VASCULITIS

Makol A, Matteson EL, Warrington KJ. Rheumatoid

vasculitis: an update. Curr Opin Rheumatol. 2015

Jan;27(1):63-70.

• Presentation: purpuric papules, macules,

retiform purpura, cutaneous ulceration, livedo,

rarely urticaria

– Systemic: fever, weight loss, myalgias,

arthralgias, segmental necrotizing and

crescentic glomerulonephritis, with pulmonary

involvement, pulmonary capillaritis, vasculitis

neuropathy, eye disease

• Pathology: necrotizing LCV

• Laboratory findings: ANCA + (70%), p-ANCA >

c-ANCA

• Treatment: systemic corticosteroids

– Localized: TMP/SMX + corticosteroids

– Generalized: MTX + CS

– Organ involvement: cyclophosphamide then MMF,

MTX, or azathioprine, IVIG and anti-TNF

(refractory)

MICROSCOPIC POLYANGIITIS

Andrews’ Diseases of the Skin 11th edition.

Bolognia 3rd edition

• Rare, potentially life-threatening PR3-ANCA

associated necrotizing vasculitis of small to medium-sized vessels

and extravascular necrotizing granulomatous inflammation

• F>M; peak age 45-65 years

• Triad

– 1) Necrotizing granulomatous inflammation of upper &

lower respiratory tracts

– 2) Glomerulonephritis

– 3) Necrotizing small to medium-vessel vasculitis

• Presentation:

– Palpable purpura followed by oral ulcers/friable gums

“strawberry gums”

– Painful SQ nodules resemble pyoderma gangrenosum

– Upper or lower respiratory tract involvement

– Glomerulonephritis

– Other: musculoskeletal, ocular, neurological, GI, and cardiac

– Saddle-nose deformity due to mucosal necrotizing

granulomas

GRANULOMATOSIS WITH POLYANGIITIS

R. Heera, Kanaram Choudhary, V. T. Beena, and Simon.R.

Strawberry gingivitis: A diagnostic feature of gingival

Wegener's granulomatosis. Dent Res J (Isfahan). 2012 Dec;

9(Suppl 1): S123–S126.

• Labs:– (+) c-ANCA in 80-90%, generalized

disease, 60% in localized– RF, ESR, CRP, anemia,

leukocytosis, anti-MPO Ab in 10%, proteinuria, RBC casts

• Pathology: – LCV-like changes, palisading

granulomas, granulomatous vasculitis surrounding foci of basophilic necrobiosis

• Treatment: – Corticosteroids + cyclophosphamide

= 75% remission– Corticosteroids + rituximab may be

equally effective

GRANULOMATOSIS WITH POLYANGIITIS


Schaffer. Dermatology. Philadelphia: Elsevier

Saunders, 2012. 3rd edition

• Presentation: palpable purpura,

subcutaneous nodules of extremities and

scalp, firm non-tender purpuric papules of

fingertips, urticaria

• 3 phases:1. Initial: allergic rhinitis, nasal polyps, asthma (35 yo)

2. Secondary (2-12 years later): fever, eosinophilia,

with pneumonia and gastroenteritis

3. Tertiary: diffuse angiitis of the liver, spleen, kidneys,

intestines, and pancreas, mononeuritis multiplex

common

• Medication triggers: vaccination,

desensitization, leukotriene inhibitors,

azithromycin, nasal fluticasone, rapid d/c

corticosteroids

• Death from CHF d/t granulomatous

inflammation of myocardium

CHURG-STRAUSS SYNDROME

Andrews’ Diseases of the Skin 11th edition.

Bolognia 3rd edition

• Laboratory findings: peripheral

eosinophilia, p-ANCA (anti-

myeloperoxidase ab) positive, c-ANA (anti-

PR3) sometimes positive

• Pathology: small and medium LCV, Wells

syndrome with flame figures, palisaded

granulomas lacking giant cells with central

eosinophils

• Treatment: corticosteroids,

cyclophosphamide with corticosteroids if

neuro, renal, myocardial, or

gastrointestinal involvement

– MTX or other steroid-sparing agents can be

used to maintain remission

CHURG-STRAUSS SYNDROME

Ratzinger et al. Eosinophilic leukocytoclastic vasculitis: a

spectrum ranging from wells’ syndrome to Churg-Strauss?

European Journal of Dermatology. 2014 Sept-Oct. 24(5):

603-10.

• HLA-B51

• Diagnostic Criteria:

– Oral ulcers 3 times in 12 month period plus 2 of

below

• Recurrent genital ulcers

• Positive pathergy test

• Uveitis, retinal vasculitis

• Skin findings: Ulcerations, acneiform,

papulopustular, EN-like

• Clinical Features:

– Painful

– CNS lesions (MS-like)

– Thrombophlebitis

– Thrombosis of SVC

– Asymmetric, non-erosive polyarthritis

• Histology:

– Vasculitis may involve small and medium vessels

– Predominantly neutrophilic infiltrate

• Treatment:

– Colchicine, dapsone, thalidomide, TNF-inhibitors

BEHCET’S DISEASE

Rokutanda R, Kishimoto M, Okada M. Update on the diagnosis

and management of Behçet’s disease. Open Access

Rheumatology : Research and Reviews. 2015;7:1-8.

doi:10.2147/OARRR.S46644.

Thank You

vasculitides & vaso-occlusive disorders · vasculitides & vaso-occlusive disorders ......

Documents