Cutaneous Vascular Diseases

1. Cutaneous Vascular Diseases JoAnne M. LaRow, DO June 7, 2004

2. Vasculitis • Clinicopathologic process characterized by inflammation and necrosis of blood vessels • Blood vessel size is useful in classifying these disorders

3. Idiopathic cutaneous small-vessel vasculitis Henoch-Schönlein purpura Acute hemorrhagic edema of infancy Urticarial vasculitis Essential mixed cryoglobulinemia Waldenström’s hypergammaglobulinemic purpura Collagen vascular associated Rheumatoid nodules with vasculitis Hyperimmunoglobulinemia D syndrome Familial Mediterranean fever Classificationcutaneous small-vessel disease

4. Erythema elevatum diutinum Granuloma faciale Reactive Hansen’s disease Septic vasculitis Classificationcutaneous small-vessel disease

5. Polyarteritis nodosa Benign cutaneous forms Systemic form (including microscopic variant) Granulomatous vasculitis Limited Wegener’s granulomatosis Wegener’s granulomatosis Allergic granulomatosis (Churg-Strauss) Medium-vessel necrotizing vasculitis

6. Large-vessel vasculitis • Giant-cell arteritis • Takayasu’s arteritis

7. Cutaneous small-vessel vasculitis(leukocytoclastic vasculitis) • Palpable purpura is the hallmark • Pinpoint to several centimeters • Early on lesion may not be palpable • Papulonodular, vascular, bullous, pustular or ulcerated forms may develop • Predominate on the ankles and lower legs • Affect mainly dependent areas

8. Cutaneous small-vessel vasculitis(leukocytoclastic vasculitis) • Mild pruritis, fever, malaise, arthralgia and/or myalgia may occur • Typically resolve in 3 to 4 weeks • Residual postinflammatory hyperpigmentation may be seen • Self-limiting • May recur or become chronic • Hemorrhagic vesicles or bullae may develop

9. Cutaneous small-vessel vasculitis(leukocytoclastic vasculitis) • Urticaria-like lesions are next most common • They have less evanescence than ordinary hives • Usually resolve after a few days • Edema, especially of the ankles, is usually noted • Arthralgias may be seen • Major renal manifestation is glomerulonephritis • May have gastrointestinal involvement

10. histology • Angiocentric segmental inflammation, endothelial cell swelling, fibrinoid necrosis of blood vessel walls and a cellular infiltrate composed of neutrophils showing fragmentation of nuclei

11. pathogenesis • Many forms of small-vessel vasculitis are felt to be caused by circulating immune complexes • These lodge in vessel walls and activate compliment

12. etiolology • Types of antigens inducing immune complexes vary • Some infectious agent and drugs are well defined

13. Clinical evaluation • Detailed history and physical examination • History should focus on possible infectious disorders, prior associated diseases, drugs ingested, and a thorough review of systems • CBC, strep throat culture or ASO titer, Hep B & C serologies and ANA are a reasonable initial screen

14. treatment • Initial treatment should be nonaggressive • Rest and elevation of the legs • Analgesics, a good diet, and avoidance of trauma or cold • Any identified antigen or drug should be eliminated

15. A variety of systemic treatments may be required for severe, intractable or recurrent disease • For disease limited to the skin NSAIDs, antihistamines, colchicine and dapsone • Systemic corticosteroids for those with systemic manifestations or necrotic lesions • Immunosuppressive agents for rapidly progressive course and severe systemic involvement

17. A. classical purpuric papules & papules on lower leg • B. CSVV evolving to form confluent hemorrhagic plaque on posteroir ankle • C. lesions in various stages of evolution

18. Subtypes of Small-Vessel Vasculitis

19. Henoch-Schönlein Purpura(HSP) (anaphylactoid purpura) • Characterized by intermittent purpura, arthralgia, abdominal pain, and renal disease • Typically purpura appears on the extensor surfaces of the extremities • Become hemorrhagic within a day and fades in 5 days • New crops appear over a few weeks

20. Henoch-Schönlein purpura(HSP) • Primarily occurs in male children • Peak age 4-8 years • Adults may be affected • A viral infection or streptococcal pharyngitis are the usual triggering event • In about 40 % of the cases the cutaneous manifestations are preceded by mild fever, headache, joint symptoms, and abdominal pain for up to 2 weeks

21. Henoch-Schönlein Purpura(HSP) • May be pulmonary hemorrhage • Abdominal pain and GI bleeding may occur at any time • GI radiographs may show “spiking” or a marbled “cobblestone” appearance • Renal manifestations may occur in 25% or more

22. Henoch-Schönlein Purpura(HSP) • The long-term prognosis in children with gross hematuria is very good; however, progressive glomerular disease and renal failure may develop in a small percentage • IgA, C3 and fibrin depositions have been demonstrated in biopsies of both involved and uninvolved skin by immunofluorescence techniques

23. Henoch-Schönlein purpura(HSP) • Treatment is supportive • Duration of illness is typically 6 to 16 weeks • Between 5 and 10 % of patients will have persistent or recurrent disease • Antispasmodics, antibiotics, and antiinflammatory drugs, including systemic corticosteroids • Plamaphoresis in severe cases

27. Acute Hemorrhagic edema of infancy • AKA Finkelstein’s disease, Seidlmayer syndrome, and purpura en cocarde avec oedema • Affects children under the age of 2 with a recent history of an upper respiratory illness, a course of antibiotics of both • Children are often nontoxic in appearance • No extracutaneous involvement • Spontaneously resolves with 1-3 weeks

28. Acute Hemorrhagic edema of infancy • Abrupt onset of large cockade, annular, or targetoid purpuric lesions involving the face, ears, and extremities • Early in the course there may first be acral edema, may be nontender and asymmetrical • Low-grade fever is common, and involvement of internal organ systems is rare • Routine lab tests are nondiagnostic

29. Acute Hemorrhagic edema of infancy • Considered a variant of leukocytoclastic vasculitis with many similarities to HSP • Spontaneous recovery within a few weeks • DDX includes meningococcemia, HSP, erythema multiforme, urticaria and Kawasaki’s disease • Clinically most urgent to exclude meningococcemia

30. Acute Hemorrhagic edema of infancy

31. Multiple erythematous, nummular & targetoid plaques on an infant’s thighs

32. Urticarial vasculitis • Recurrent episodes of painful, persistent urticaria &/or angioedema • May be associated with constitutional symptoms & arthritis • Pts with hypocomplementemia are more likely to have systemic involvement • Associated disorders are autoimmune connective tissue dx & viral infections

33. Urticarial vasculitis • Three clinical features distinguish the skin lesions of urticarial vasculitis from urticaria • 1. Lesion are usually painful rather than pruritic • 2. Lesions last longer than 24 hours • 3. On healing there is postinflammatory hyperpigmentation

34. Clinical features • Similar in hypocomplementemic & normocomplementemic variants • Erythematous indurated wheals, angioedema, or macular erythema • Extracutaneous manifestations include :fever, malaise, lymphadenopathy, hepatosplenomegaly, arthralgias & glomerulonephritis, hepatosplenomegaly, arthritis & glomerulonephritis, GI ( nausea, vomiting, diarrhea, abdominal pain), respiratory (laryngeal edema, SOB, COPD), ocular (conjunctivitis, episcleritis, uveitis)-more common in hypocomplementemic variant

35. Several erythematous urticarial plaques on the foot & ankle

36. Urticarial vasculitis-tx • Pts with hypocomplementemic UV respond to oral corticosteroids • Hydroxychloroquine sulfate, colchicine, dapsone, NSAIDs or pentoxifylline • Some pts require a combination of therapies with antihistamines

37. Hyperimmunoglobulinemia D syndrome • Characterized by recurrent high-spiking fevers with abdominal distress, diarrhea, vomiting, headache, and arthralgias • Up to 79% of HID syndrome will have cutaneous findings • Outside of neonatal period associated with papulopustules on face, scalp, ‘cold’ abscesses, dermatitis, recurrent pneumonias with pneumatocele formation, osteopenia & retention of deciduous teeth • Genetic linkage on chromosome 4 has been reported

38. Hyperimmunoglobulin E syndrome • Multisystem immunologic disorder • Vesicles or papulopustular eruption or recurrent pustules occurs early in infancy with crusting on face, scalp, neck & upper torso • Usually associated with high levels of IgE (over 2000 IU/ml) &eosinophilia • Elevated levels of IgE may not be present in early infancy & may fluctuate independent of severity of dx

39. Hyperimmunoglobulinemia D syndrome • Lymphadenopathy and splenomegaly are common • Age of onset usually under 10 years • Marked elevations in serum IgD are characteristic • No preferred treatment • Colchicine • dapsone

40. Familial Mediterranean fever • A periodic fever syndrome that may be confused with HID syndrome • Has been reported to affect Sephardic Jews, Armenians, and individuals of Arabian descent • Onset usually under 10 years • Cutaneous findings consist of erysipelas-like erythema showing a sharp border

41. Familial Mediterranean fever • Affects the lower extremities on the dorsa of the feet , over the ankles, and sometimes the knees • Erysipelas-like erythema is considered characteristic, however this occurs in only 3 to 46% of patients • Arthralgias, peritonitis, and constipation may occur • No lymphadenopathy, and no elevation of IgD

42. Familial Mediterranean fever • On skin biopsy there is most frequently leukocytoclastic vasculitis • Defect at chromosome 16 polymorphic locus RT70 • Tx - colchicine

43. Erythema elevatum diutinum • A rare condition considered to be a chronic fibrosing leukocytoclastic vasculitis • Classically multiple yellow papules develop over the joints, particularly the elbows, knees, hands, and feet • May involve the buttocks and areas over the Achilles tendon • With time the p • Initially noduleas are soft & mobile • Papules take on a doughy to firm consistency and develop red to purple

44. Erythema elevatum diutinum Symmetric, persistent, red-purple, red-brown, or yellowish papules, plaques or nodules Favor extensor surfaces of joints-especially hands & knees, & buttocks & achilles tendon Mucous membranes usually spared Face & ears usually affected Lesions may involute & leave hyper-or hypopigmented atrophic scars Lesions may be painful, aching, burning, or asymptomatic Dx course is variable;can last 5-35 yrs;periods of waxing & waning;TOC:Dapsone

45. Erythema elevatum diutinum

46. histology • Acute lesions show necrotizing LCV with neutrophils in upper & mid-dermis; may have prominent eos • Chronic lesions show fibrosis, capillary proliferation, & macrophage, plasma cell & lymphocytic infiltrate • Older lesions may have intracellular & extracellular cholesterol deposits-giving the appearance of yellow xanthomas

47. Top: multiple symmetric red-brown nodules & plaques on extensor surface of digits • Bottom: red-brown palques & nodules of concha, antihelix & of the ear

48. Early stage: dense perivascular infiltrate of neutrolphils admixed with lymphs & histiocytes • Late-stage: minimal inflammatory infiltrate & marked perivascular fibrous thickening

49. Granuloma faciale • Characterized by brownish-red, infiltrated papules, plaques, and nodules • Involves facial areas, particularly the nose • Typically healthy middle aged white men • Pathology of GF is identical to EED

50. Granuloma faciale • Often resistant to tx • Intralesional corticosteroids(first line non-scarring option • Cryotherapy, dermabrasion, electrosurgery, surgical excision • Topical corticosteroids • Dapsone, colchicine, antimalarials • Topical PUVA and gold injections