Management of Pyoderma Gangrenosum Mentoring in IBD XVII

Transcription

1 Management of Pyoderma Gangrenosum Mentoring in IBD XVII Scott Walsh MD PhD FRCPC Division of Dermatology Sunnybrook Health Sciences Centre University of Toronto

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7 Pyoderma Gangrenosum: A pathological abundance of neutrophils in the absence of infection. Most common systemic association is IBD. Perianal and colonic disease. Other associated EIMs: uveitis, arthritis, spondylitis Women, lower extremities. Prevalence CD 1.3% UC 0.8% Older age and typically longer into disease course. Ko et al J. Cutan. Pathol. In press; Broswell et al J. Am. Acad. Dermatol. 73: 691-8; Weizman et al Inflamm. Bowel Dis. 20: ; Bernstein et al Am. J. Gastroenterol. 96:

8 Variation Pyoderma Gangrenosum (PG): 10 Variations on the theme of PG: Ulcerative (Classic) Pustular Bullous Superficial granulomatous Peristomal Post-Surgical Drug-Induced Syndromic Pyostomatitis vegetans Extracutaneous Notes Undermined borders IBD, arthritis, vasculitis "creeping eruption of IBD" (UC) Malignancy-associated Usually no association Pathergy or irritation around site (CD) Breast and abdomen (CD) GSF, GMCSF, PTU, IFN PAPA, PASH, PAPASH, "snail-track appearance" (UC) Lungs, bones, liver, CNS, renal Ko et al J. Cutan. Pathol. In press; Gade et al Resp. Medicine 109: ; Broswell et al J. Am. Acad. Dermatol. 73: 691-8; Weizman et al Inflamm. Bowel Dis. 20: ; Bernstein et al Am. J. Gastroenterol. 96:

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25 Barbosa et al J. Am. Acad. Dermatol. In press.

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27 Pyoderma Gangrenosum (PG): Peristomal versus post-surgical PG: Periostomal Post-Surgical Time to Onset 5.2 months 11 days Associated IBD 93% 11% Recurrence rate 61% low Barbosa et al J. Am. Acad. Dermatol. In press; Ohashi et al J. Dermatol. 42:

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29 Pyoderma Gangrenosum (PG): Diagnostic Criteria for Classic PG: MAJOR (both): Rapid progression of painful, necrolytic ulcers with an irregular, violaceus undermined border. Other causes of cutaneous ulceration have been excluded. MINOR (2/4): History suggestive of pathergy or clinical finding of cribriform scarring. Systemic disease associated with PG (50-78%) IBD, arthritis, hematologic malignancy, IgA paraprotein, myelodysplasia, vasculitis) Histopathology compatible (sterile dermal neutrophilia, +/- mixed inflammation, +/- lymphocytic vasculitis. Response to systemic corticosteroids. Su et al Int. J. Dermatol. 43:

30 Pyoderma Gangrenosum (PG): Differential of PG: Infections Vasculitis Fungal, mycobacterial, tertiary syphilis Granulomatosis with polyangiitis, Behcet's. Immunodeficiencies Leukocyte adhesion deficiency, CGD Toxins (loxoscelism) Malignancies SCC, lymphomas Metastatic or dystrophic calcification Calciphylaxis

31 Atypical mycobacterial infection

32 vasculitis

33 Calcific uremic arteriopathy (calciphylaxis)

34 SCC

35 Gamma Delta T-cell lymphoma

36 Pyoderma gangrenosum Usually biopsy edge of lesion: Culture Histopathology Intralesional triamcinolone acetonide to biopsy site. Pathergy

37 Approach to Treatment: Suppression of Inflammatory Disease Activity: Topical Intralesional Systemic Promotion of Wound Healing. Treatment of Secondary Infections. Treatment of Associated Disease. Control of Pain. Patel et al Acta Derm. Venereol. 95:

38 Approach to Treatment: Suppression of Inflammatory Disease Activity: Topical: Class I-II corticosteroids Clobetasol propionate, halobetasol Betamethasone dipropionate, fluocinonide Topical calcineurin inhibitors Tacrolimus, pimecrolimus Topical dapsone Topical sodium cromoglycate Otic or optic formulations Patel et al Acta Derm. Venereol. 95: ; Handler et al J. Drugs Dermatol.10: ; Wenzel et al Dermatol. 205:

39 Approach to Treatment: Suppression of Inflammatory Disease Activity: Intralesional: Triamcinolone acetonide mg/ml into any active or undermined edges q2weeks. Patel et al Acta Derm. Venereol. 95:

40 Approach to Treatment: Suppression of Inflammatory Disease Activity: Systemic: Prednisone 1 mg/kg/day +/- pulse IV steroids. Cyclosporine 2-5 mg/kg/day TNF alpha inhibitors (Infliximab, Adalimumab) Mycophenolic acid/mycophenolate mofetil Intravenous immunoglobulin (2 g/kg initiation and 1 g/kg q4weeks). Dapsone, sulfasalazine, colchicine. Ustekinumab, Gevokizumab, Anakinra, Canakinumab, Chokoeva et al Wien. Med. Wochenschr. In press; Greb et al Dermatol. Therapy. In press; Peyrin- Biroulet et al Clin. Gastroentterol. Hepatol. In press; Patel et al Acta Derm. Venereol. 95: ; Marzano et al Inflamm. Bowel Dis. 20:

41 Approach to Treatment: Promotion of Wound Healing: Compression to reduce edema is key principle. ABI's +/- oxygen saturations +/- toe pressures. Short-stretch (compromised arterial supply) High-stretch (minimal vascular disease) Hyperbaric oxygen. Chiang et al Ostomy Wound Manage. 62:32-6.

42 Approach to Treatment: Treatment of Secondary Infections. Dilute acetic acid washes (1:5 to 1:10 as tolerated). Alginates if exudative. Broad spectrum coverage. Activated silver, crystal violet. Bacterial binding resins Systemic antibiotic coverage based on deep swabs or biopsy for culture.

43 Approach to Treatment: Treatment of Associated Disease. Favours addition of TNF alpha inhibition. Usually immunosuppressive agent added to prolong life of TNF alpha inhibitor. Mycophenolate mofetil.

44 Approach to Treatment: Control of Pain. Short-acting titrated to long-acting with short-acting breakthroughs. Important for compression therapy.

45 Typical Treatment for Severe PG: Systemic: Topical and wound care: Prednisone 1 mg/kg/day x 4 weeks and then tapered by 5 mg weekly. Cyclosporine 4 mg/kg/day tapered by 1 mg/kg/day q4weeks. TNF alpha inhibitor. Mycophenolate mofetil added as cyclosporine tapering. Acetic acid washes 1:8 with dressing changes. Sodium cromoglycate drops. Silver alginate. 3-layer compression (30-40 mm Hg). Swabs for bacterial coverage if necessary. Intralesional - Triamcinolone acetonide into active edges q2-4 weeks. Pain Control - Short-acting morphine transition to long-acting with breakthrough.