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Home , Capillaritis, Palpable purpura, Polyarteritis nodosa, Urticarial vasculitis, Vasculitis

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

A. Vasculitis/Leukocytoclastic Vasculitis B. Henoch-Schonlein C. Acute Hemorrhagic Edema of Infancy D. E. Cryoglobulinemic Vasculitis F. Elevatum Diutinum HYPERSENSITIVITY VASCULITIS / CUTANEOUS LEUKOCYTOCLASTIC VASCULITIS (LCV)

• All ages & sexes, MC in adults • Etiology: deposition • Presentation: , erythematous , urticarial lesions involving dependent areas – Koebner phenomenon – , weight loss, with flares • Pathology: – H&E: LCV, karyorrhexis, extravasated RBC – DIF: C3, IgM, IgA and/or IgG granular deposits in vessels

Bolognia, Jean, Joseph L. Jorizzo, and Julie V. Schaffer. Dermatology. Philadelphia: Elsevier Saunders, 2012. Print. HYPERSENSITIVITY VASCULITIS / CUTANEOUS LEUKOCYTOCLASTIC VASCULITIS (LCV)

• Secondary LCV • Idiopathic (50%) • (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,

Bolognia, Jean, Joseph L. Jorizzo, and Julie V. Schaffer. Dermatology. Philadelphia: Elsevier Saunders, 2012. Print. HENOCH-SCHONLEIN PURPURA IGA VASCULITIS

• MC children • Etiology: bacterial & viral • Presentation: palpable purpura, , , renal disease • Pathology: – H&E: LCV – DIF: IgA vasculitis • Treatment: systemic corticosteroids, immunosuppressants, ACE-I • Prognosis: monitor for chronic renal insufficiency

Gaskill, Neil; Guido, Bruce; & Mago, Cynthia. (2016). Recurrent adult onset Henoch-Schonlein Purpura: a case report. Dermatology Online Journal, 22(8). doj_32191. ACUTE HEMORRHAGIC EDEMA OF CHILDHOOD

• 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, • Treatment: Resolves spontaneously in 1-3 weeks

Mreish S, Al-Tatari H. Hemorrhagic Lacrimation and Epistaxis in Acute Hemorrhagic Edema of Infancy Case Rep Pediatr. 2016;2016:9762185. URTICARIAL VASCULITIS

• Adults, peak 50s, F>M • Etiology: unknown • Variants: – Normocomplementemic – Hypocomplementemic • Associations: – CTD (Sjögren’s, SLE) – – – Infections (HBV, HCV, EBV, Lyme) – Medications – Hematologic & solid malignancies: colon & renal cell

James W, Berger T, Elston D. (2011) Andrews’ Diseases of (11th ed.) Edinburgh, London, New York, Oxford, Philadelphia, St Louis, Sydney, Toronto, Elsevier Inc. URTICARIAL VASCULITIS

• Presentation: – Erythematous annular or targetoid wheals resemble urticaria3 clinical → progress features to purpura distinguish skin lesions of urticarial with residual – Favor trunk or proximalvasculitis from true urticaria: extremities – > 24 hours –1.RecurrentLesions lesions are often painful, rather than pruritic. –2.PainfulLesions or burning>24 hrs and are fixed, rather than migrating. – Systemic findings: angioedema, 3.arthralgias,Post-inflammatory abdominal or chest purpura or hyperpigmentation. pain, fever, dyspnea, , & 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. URTICARIAL VASCULITIS

• Diagnosis: skin – 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, , mycophenolate mofetil, • 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. CRYOGLOBULINEMIC VASCULITIS

• Palpable purpura MC • Other findings: erythematous papules, ecchymoses, nodules, urticaria, , necrosis, ulcerations, bullae • Extracutaneous findings: – Arthralgias/ (70%) – Peripheral sensory neuropathy (40%) – GI symptoms or hepatitis (30%) – Membranoproliferative glomerulonephritis (25%)

1Berera SR et al. A Rare Case of -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 . Journal of Clinical and Diagnostic Research 2016;10(4):18-19. CRYOGLOBULINEMIC VASCULITIS

• 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 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 • 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 MEDIUM-VESSEL VASCULITIS A. (benign & systemic)

MIXED (MEDIUM & SMALL) VESSEL VASCULITIS

A. Connective Tissue Disease Associated (usually rheumatoid vasculitis) B. Septic Vasculitis C. ANCA-Associated 1. 2. Granulomatosis with Polyangiitis 3. Allergic Granulomatosis (Churg-Strauss) POLYARTERITIS NODOSA

• 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

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 () & medications • Pathology: Segmental necrotizing vasculitis in subcutaneous tissue • Treatment – Classic PAN – systemic corticosteroids (1 mg/kg/day of ) – 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 RHEUMATOID VASCULITIS

• Rare, late 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, 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

Makol A, Matteson EL, Warrington KJ. Rheumatoid vasculitis: an update. Curr Opin Rheumatol. 2015 Jan;27(1):63-70. MICROSCOPIC POLYANGIITIS

• 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 , 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)

Andrews’ Diseases of the Skin 11th edition. Bolognia 3rd edition GRANULOMATOSIS WITH POLYANGIITIS

• Rare, potentially life-threatening PR3-ANCA associated necrotizing vasculitis of small to medium-sized vessels and extravascular necrotizing granulomatous • 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 – Upper or lower respiratory tract involvement – Glomerulonephritis – Other: musculoskeletal, ocular, neurological, GI, and cardiac – Saddle-nose deformity due to mucosal necrotizing

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. GRANULOMATOSIS WITH POLYANGIITIS

• Labs: – (+) c-ANCA in 80-90%, generalized disease, 60% in localized – RF, ESR, CRP, , , anti-MPO Ab in 10%, , 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

Bolognia, Jean, Joseph L. Jorizzo, and Julie V. Schaffer. Dermatology. Philadelphia: Elsevier Saunders, 2012. 3rd edition CHURG-STRAUSS SYNDROME

• Presentation: palpable purpura, subcutaneous nodules of extremities and scalp, firm non-tender purpuric papules of fingertips, urticaria • 3 phases: 1. Initial: , nasal polyps, (35 yo) 2. Secondary (2-12 years later): fever, , 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

Andrews’ Diseases of the Skin 11th edition. Bolognia 3rd edition CHURG-STRAUSS SYNDROME

• Laboratory findings: peripheral eosinophilia, p-ANCA (anti- 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 • Treatment: corticosteroids, cyclophosphamide with corticosteroids if neuro, renal, myocardial, or gastrointestinal involvement – MTX or other steroid-sparing agents can be used to maintain remission

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. BEHCET’S DISEASE • HLA-B51 • Diagnostic Criteria: – Oral ulcers 3 times in 12 month period plus 2 of below • Recurrent genital ulcers • Positive pathergy test • Uveitis, • Skin findings: Ulcerations, acneiform, papulopustular, EN-like • Clinical Features: – Painful – CNS lesions (MS-like) – – of SVC – Asymmetric, non-erosive • Histology: – Vasculitis may involve small and medium vessels – Predominantly neutrophilic infiltrate • Treatment: – Colchicine, dapsone, thalidomide, TNF-inhibitors

Rokutanda R, Kishimoto M, Okada M. Update on the diagnosis and management of Behçet’s disease. Open Access : Research and Reviews. 2015;7:1-8. doi:10.2147/OARRR.S46644. Thank You