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Vasculopathic Diseases I
Vasculopathic Diseases I Eric Millican, WUMS IV February 8, 2010 1 Classification • Pseudovasculitis – Erythrocyte extravasation – +/- Thrombi – No vascular necrosis • Vasculitis – – – – Vessel wall necrosis, hyalinization, fibrin deposition Inflammatory cell invasion Thrombi Nuclear dust • Miscellaneous 2 Pseudovasculitis • Compared to true vasculitic diseases: – Isolated vascular lesions – Livedo reticularis – Absence of inflammatory markers 3 Classification Pseudovasculitis Mechanistic Morphologic • Non-inflammatory Purpuras – RBC Extravasation without inflammation • Vascular Occlusive Diseases – Obliteration of small vessel lumen • Urticarias – Plasma +/- cellular leakage from dermal vessels Carlson and Chen 4 Side Note Cutaneous Blood Supply 5 Non-inflammatory Purpuras • Trauma / Blood Vessel Incompetence – – – – – – – Trauma Solar (Senile) purpura Pigmented purpuric dermatoses Idiopathic thrombocytopenic purpura Scurvy Autoerythrocyte sensitization syndrome +/- Drug / Arthropod / Viral eruptions • Vessel Wall Pathology – Calciphylaxis – Amyloidosis – Radiation Arteriopathy 6 Non-inflammatory Purpuras Solar / Senile / Bateman’s / Actinic Purpura • Pathogenesis • Loss of collagen supporting dermal vessels + minor trauma • Clinical – Elderly patients – Ecchymoses on forearm extensors & hands – Slow resolution without usual bruising color changes Rosen • Histology – Superficial dermal erythrocyte extravasation – Solar elastosis – Dermal collagen atrophy – No inflammation Carlson and Chen 7 Non-inflammatory Purpuras Pigmented Purpuric Dermatoses Carlson and Chen • Pathogenesis – Chronic superficial “capillaritis” – Associated with various allergens, medications, Hep B/C – 2/2 autoantibodies, delayed hypersensitivity, and/or capillary fragility – Relation to CTCL ? • Clinical – Young adults/children – Red, brown, or yellow macules/patches Progressive pigmentary dermatosis (Schaumberg’s Disease) Most common Cayenne pepper petechiae Symmetric, pretibial Eczematous purpura (of Doucas and Kepatanakis) Pruritus, scaly Subtype of Schaumberg’s Purpura annularis telangiectodes (Majocchi’s disease) Annular pupura Perifollicular red lesions Lichenoid purpura (Gougerot-Blum purpura) Plaque-like lesions Symmetric, lower legs Lichenoid infilitrate Lichen aureus Unilateral, gold-yellow macule Trunk / UE, can be LE Hoesly et al Sardana et al 8 Non-inflammatory Purpuras Pigmented Purpuric Dermatoses • Histology – Normal epidermis +/- focal spongiosis – Superficial dermal lymphohistiocytic infiltrate (esp. lichen aureus) – Lymphoid (CD4 > CD1a) pericapillary infiltrate – “Top heavy” hemosiderin – Can have CTCL appearance but no atypia or dermal fibrosis Sardana et al 9 Non-inflammatory Purpuras Calciphylaxis • Clinical – Associated with renal failure + dialysis, hyperparathyroidism – Calcium-phosphate product > 60 – Ulceration and geographic necrosis – Indurated, gritty skin – High mortality • Histology – Circumferential calcification of small vessel walls • Black deposits with Von Kossa stain – Vascular thrombosis +/- intimal hyperplasia Carlson and Chen 10 Non-inflammatory Purpuras Radiation Arteriopathy • Pathogenesis – ~ 5 years: Intimal injury and mural thrombosis – ~10 years: progressive vessel wall fibrosis – ~20 years: premature atherosclerosis • Histology – Ulceration and superficial necrosis – Sclerotic collagen bundles – Decreased vessel number – Deep vessel myointimal proliferation +/- hyaline – Enlarged, reactive appearing endothelial cells – +/- Fibrinous necrosis of vessel walls Carlson and Chen – Abundant dermal hemorrhage – Mild perivascular lymphocytic infiltrate, including vessel wall involvement 11 Non-inflammatory Purpuras Autoerythrocyte sensitization / Gardner-Diamond syndrome • Pathogenesis – Autoimmune vs RBC phosphatidylserine • Clinical – Rare, 162 cases worldwide – Women, usually <30 – s/p psychic stress or minor trauma/exercise – Comorbid psychopathology – Prodromal fatigue stinging/itching painful infiltrated pink/red plaques in 4-5 hrs ecchymosis with decreasing pain over 24-36 hrs – Usually limited to skin, LE > others • Diagnosis – Autoerythrocyte sensitization test – Autologous RBCs typical lesions in ~ 24 hr – Normal coagulation profile • Histology = Pseudovasculitis Ivanov et al 12 Vascular Occlusive Diseases • • • • • • • Warfarin Necrosis Atrophie Blanche DIC / Pupura Fulminans Cryoglobulinemia Type I Cholesterol Embolization Antiphospholipid Syndrome Sneddon’s Syndrome 13 Vascular Occlusive Diseases • Histology – – – – Epidermis normal to ulcerated Thrombi in various sized vessels +/- hemorrhage Mild perivascular lymphocytic infiltrate Wiedermann 14 Vascular Occlusive Diseases Disorder Depth Thrombus Atrophie Blanche Superficial Fibrin DIC Superficial +/- deep Fibrin Purpura Fulminans Superficial and deep Fibrin TTP Superficial Fibrin-platelet Thrombocythemia Superficial and deep Fibrin-platelet Antiphospholipid Syndrome Deep +/- superficial Fibrin-platelet Warfarin Necrosis Deep Fibrin-platelet Cryoglobulinemia Type I Superficial Eosinophilic Ig Cholesterol Emboli Deep Cholesterol crystals Sneddon’s Syndrome Deep Fibrin-inflammatory cells Subendothelial cells 15 Vascular Occlusive Diseases Warfarin Necrosis • Pathogenesis – Protein C/S depletion initial pro-coagulant effect • Clinical – Fatty areas of obese, middle-aged women – Vesicles and urticaria ecchymosis blister & necrosis – Purple toes • Histology – Fibrin-platelet thrombi in deep dermis – +/- hemorrhage and infarction Nazarian et al Carlson and Chen 16 Vascular Occlusive Diseases Antiphospholipid Syndrome • Pathogenesis – Antiphospholipid antibodies: Lupus anticoagulant, anticardiolipin, or anti-b2I • Clinical – TIA / CVA, DVT, PE, fetal loss – Cutaneous signs: Livedo reticularis (#1), purpura, digital necrosis, subungual splinter hemorrhages • Histology – +/- subepidermal blister – Vascular thrombi in deep vessels • Small vessels involved in necrotic lesions • Often need multiple deep biopsies – +/- Disruption of the elastic lamina – +/- Reactive angioendotheliomatosis – Similar findings in various coagulopathies Carlson and Chen 17 Vascular Occlusive Diseases Sneddon’s Syndrome • Pathogenesis – ? Endothelial autoantibodies – ? Subset of APLS • Clinical – – – – Middle-aged women Diffuse livedo reticularis LE ulcers Systemic arterial thrombi including cerebral microcirculation • Histology – Multiple biopsies in erythematous areas needed – Deep vessels with early endothelitis fibrin-inflammatory cell thrombi subendothelial cell proliferation 18 Vascular Occlusive Diseases Atrophie Blanche / Livedoid Vasculopathy / PURPLE • Pathogenesis – Decreased fibrinolysis fibrin thrombi • Clinical – Women, middle-age or older – Telangiectatic, purpuric papules/plaques painful punched-out ulcers atrophic, stellate scars recurrent ulceration – Ankles/feet +/- forearm extensors – Associated with various hypercoaguable states – If no evidence of coagulation disorders, suspect true vasculitis Hairston et al Acland et al 19 Vascular Occlusive Diseases Atrophie Blanche • Histology – Epidermis atrophic +/spongiosis – Fibrin in mid/upper dermal vessel walls and lumen – Dermal sclerosis in late lesions – Stasis changes (nodular angioplasia or “cannonball tufting”) of superficial dermal vessels – Actual vasculitis suggests ulceration due to CTD • DIF – Broad bands fibrin, Ig & C’ at vessel walls Acland et al 20 Vascular Occlusive Diseases DIC • Pathogenesis – Systemic activation of coagulation microthrombi consumptive coagulopathy and hemorrhage – Etiology incl. infection, OB, tissue injury, vasculitis, neoplasms • Clinical – Varied cutaneous findings: petechiae, ecchymoses, bullae, acral cyanosis, gangrene • Histology – Superficial +/- deep dermal fibrin thrombi – Variable epidermal and adnexal necrosis – Mild inflammation 21 Vascular Occlusive Diseases Purpura Fulminans • Pathogenesis – DIC subtype – Associations: recent URI, surgery or childbirth, young age, asplenia – Etiology: N. meningitidis, H. influenzae, S. pneumoniae • Clinical – Children < 7 years, rarely adults – Overall mortality rate 43% – Erythematous macules central purpura necrosis – LE and buttocks – Fever, and septic shock Cerone et al • Histology – Thrombi diffusely throughout dermis – Extensive hemorrhage and necrosis +/- bullae Wiedermann 22 Vascular Occlusive Diseases TTP / Thrombocythemia • Pathogenesis – TTP: impaired fibrinolysis MAHA, thrombocythemia, neurologic + renal dysfunction, fever – Thrombocythemia = myeloproliferative • Clinical – Livedo reticularis, erythromelalgia – Petechiae and ecchymosis – Normal coagulation profile • Histology – Platelet thrombi in superficial +/- deep vessels – Variable infarction – In thrombocythemia see arterial fibromuscular intimal proliferation 23 Vascular Occlusive Diseases Cryoglobulinemia Type I • Pathogenesis – IgG, IgM or light chains – Essential or 2/2 CLL, multiple myeloma, or macroglobulinemia Weinberg et al • Clinical – Acral cyanosis and purpura – Focal ulceration – Livedo reticularis – Usually lower extremities Vila et al 24 Vascular Occlusive Diseases Cryoglobulinemia Type I • Histology – Homogenous eosinophilic, “jelly-like,” PAS (+) material in upper dermal vessels – Mononuclear perivascular infiltrate Weinberg et al 25 Vascular Occlusive Diseases Cholesterol Emboli Carlson and Chen • Pathogenesis – Direct dislodgement (surgery, angiogram or trauma) – Anticoagulants/thrombolysis weaken fibrin clot over atheromas – Spontaneous atheroembolism • Clinical – Livedo, gangrene, cyanosis, ulceration, nodules, and/or purpura – Funduscopy: Hollenhorst plaques (retinal cholesterol emboli) 26 Vascular Occlusive Diseases Cholesterol Emboli • Histology – Thrombosis of deep dermal small arteries – Biconvex, needle-shaped clefts (may need multiple sections) – Mixed perivascular infiltrate – PMNs, Eos, Lymphs, MNGC Carlson and Chen 27 Vascular Occlusive Diseases Malignant Atrophic Pustulosis (Degos Disease) Scheinfeld • Pathogenesis – Idiopathic – “Endothelial dysfunction” secondary thrombosis • Clinical – Crops small red macules white atrophic papules – Usually trunk – Eventually associated bowel (& brain) infarcts • Histology – – – – – – – Atrophic epidermis + hyperkeratosis Wedge-shaped dermal infarct Dense perivenular lymphocytic infiltrate at periphery Loss of adnexal structures Thrombus in deep arteriole Significant endothelial swelling +/- true vasculitis Dermal mucin and/or fibrosis Ball et al 28 Urticarias Clinical • Pathogenesis – Mast cells (or basophils?) histamine vasodilatation and permeability – Idiopathic in 75% chronic cases • Clinical – Pruritic erythematous wheals with central clearing appearing and resolving within 24 hours – Worse at night – Chronic if >6 weeks – Several variants • • • • • Physical – #1, cold/heat/solar/aquagenic, more persistent Cholinergic – exercise/emotion Angioedema – drug induced, +/- hives Antigen-induced – direct or via IgE Autoimmune – FcεRIα or IgE autoantibodies 29 Urticarias Histology • Histology – – – – Dermal edema Superficial small vessel dilatation Acute: PMNs & Eos in superficial vessels Late: Mixed perivascular and interstitial lymphs +/- Eos, mast cells Zembowicz 30 References • • • • • • • • • • • • • • • • • • Acland KM et al. Livedoid vasculitis: a manifestation of the antiphospholipid syndrome? Br J Dermatol. 1999;140(1):131-5. Ball E, Newburger A, Ackerman AB. Degos' disease: a distinctive pattern of disease, chiefly of lupus erythematosus, and not a specific disease per se. Am J Dermatopathol 2003;25(4):308-20. Carlson JA and Chen KR. Cutaneous pseudovasculitis. Am J Dermatopathol 2007;29(1):44-55. Cerone JB et al. Consumptive coagulopathy. eMedicine. http://emedicine.medscape.com/article/955059-media. 2009. Accessed 2/6/2010. Georgala S et al. Persistent pigmented purpuric eruption associated with mycosis fungoides: a case report and review of the literature. J Eur Acad Dermatol Venereol 2001;15(1):62-4. Hairston BR et al. Livedoid vasculopathy: further evidence for procoagulant pathogenesis. Arch Dermatol 2006;142(11):1413-8. Hoesly FJ et al. Purpura annularis telangiectodes of Majocchi: case report and review of the literature. Int J Dermatol 2009;48(10):1129-1133. Ivanov OL et al. Autoerythrocyte sensitization syndrome (Gardner–Diamond syndrome): review of the literature. J Eur Acad Dermatol Venereol 2009;23(5):499-504. Nazarian RM et al. Warfarin-induced skin necrosis. J Am Acad Dermatol 2009;61(2):325-32. Rapini RP. Practical Dermatopathology. Elsevier Mosby, 2005. Rosen, R. Dermatologic Disease Database. AOCD. http://www.aocd.org/skin/dermatologic_diseases/index.html. 2010. Accessed 2/6/2010. Sardana K, Sarkar R, Sehgal VN. Pigmented purpuric dermatoses: an overview. Int J Dermatol 2004;43(7):482-8. Scheinfeld N. Malignant atophic papulosis. Clin Dermatol 2007;32:483-487 Vila AT et al. Cutaneous ulcers with type I cryoglobulinemia treated with plasmapheresis. Eur J Dermatol 2004;14(3):186-9. Weedon D. Skin Pathology. Churchill-Livingstone, 2010. Weinberg JM et al. Purplish papules on the legs. Diagnosis: type I cryoglobulinemia in association with WM. Arch Dermatol 2000;136(10):1263-8. Wiedermann CJ. Clinical review: Molecular mechanisms underlying the role of antithrombin in sepsis. Crit Care 2006;10(1):209. Zembowicz A. How to diagnose urticaria histologically? Dermpedia. www.dermpedia.org/case/how-to-diagnose-urticara. 2009. Accessed 2/6/2010. 31