1. The Patient With Pyoderma Gangrenosum Maria T. Abreu, MD Chief, Division of Gastroenterology University of Miami Miller School of Medicine Miami, Florida

2. 2 Audience Question 1 Correct answer: b, 6% What percentage of patients with IBD have dermatologic manifestations? IBD, inflammatory bowel disease. A.1% B.6% C.20% D.50%

3. 3 Audience Question 1 Correct answer: b, 6% What percentage of patients with IBD have dermatologic manifestations? IBD, inflammatory bowel disease. A.1% B.6% C.20% D.50%

4. 4 Audience Question 2 With which of the following therapies would you initiate treatment in a patient with PG? 6-MP, 6-mercaptopurine; AZA, azathioprine; PG, pyoderma gangrenosum; TNF, tumor necrosis factor. A.Corticosteroids B.Anti-TNF therapy C.6-MP/AZA D.Topical tacrolimus

5. 5 Audience Question 2 With which of the following therapies would you initiate treatment in a patient with PG? 6-MP, 6-mercaptopurine; AZA, azathioprine; PG, pyoderma gangrenosum; TNF, tumor necrosis factor. A.Corticosteroids B.Anti-TNF therapy C.6-MP/AZA D.Topical tacrolimus

6. 6 Case Study: Linda 25-year-old female with severe colonic CD complicated by perianal disease No response to 6-MP or IFX Undergoes a diverting ileostomy due to severe perianal disease Develops PG around the ileostomy Moving the ileostomy site leads to recurrence of the PG CD, Crohn’s disease; IFX, infliximab.

7. 7 Linda Peristomal PG

8. 8 Extraintestinal Manifestations of IBD

9. 9 Dermatologic Manifestations of IBD 5.8% of patients with IBD had ≥1 skin manifestation (cohort of >2,000) –PG (0.75%) –Erythema nodosum (4%) –Psoriasis (up to 10%) –Cutaneous CD –Numerous other disorders (uncommon) Sweet’s syndrome Epidermolysis bullosa acquisita Farhi D, et al. Medicine (Baltimore). 2008;87:281-293.

10. 10 PG Epidemiology 5% of patients with UC; less common in CD –Usually pancolitis Pustular lesion –Evolves to an ulcer with undermining violaceous borders “Pathergy” worsens with trauma Clinical course may be independent of IBD Painful Correlations –Black African origin (P=0.003) –Familial history of UC (P=0.0005) –Pancolitis (P=0.03) –Permanent stoma (P=0.002) –Eye involvement (P=0.001) –Erythema nodosum (P<0.0001) UC, ulcerative colitis. Farhi D, et al. Medicine (Baltimore). 2008;87:281-293.

11. 11 PG Clinical Features Location –Lower extremity most common –Peristomal: differentiate from fistulas –Anywhere Biopsy –No pathognomonic features Exclude superinfection

12. 12 Early PG

13. 13 Early PG (cont’d)

14. 14 Multiple PG Lesions Mid-Stage

15. 15 Advanced PG

16. 16 Advanced PG (cont’d)

17. 17 Peristomal PG

18. 18 PG Treatment Options Treating extraintestinal manifestations should be part of treating the underlying CD Variety of options, not much data –Topical steroids/topical tacrolimus –Anti-TNF therapy –Corticosteroids –Cyclosporine or oral tacrolimus acutely –6-MP or AZA may be needed for chronic lesions –Thalidomide

19. 19 PG Healing Pre- and Post-Treatment PretreatmentPost-Treatment

20. 20 PG Healing Identifying Remission No ImprovementRemission Brooklyn TN, et al. Gut. 2006;55:505-509.

21. 21 Treatment of PG IFX a P =0.025. Brooklyn TN, et al. Gut. 2006;55:505-509. Placebo (n=17) IFX 5 mg/kg (n=13) Open-label IFX 5 mg/kg (n=29) Improvement at Week 2, % 0 20 40 60 80 6 46 a Results at Week 6, % RemissionImprovement 0 20 40 60 80 69 21

22. 22 Treatment of PG Cyclosporine 11 patients with steroid-refractory PG IV cyclosporine administered –4 mg/kg per day –7 to 22 days IV, intravenous. Friedman S, et al. Inflamm Bowel Dis. 2001;7:1-7. All patients experienced closure of PG –Mean time to response, 4.5 days –Mean time to closure, 1.4 months 9 patients able to discontinue steroids

23. 23 Summary Extraintestinal manifestations of IBD generally mirror disease activity and may respond to treatment of underlying disease PG may respond to biologics and immunomodulators Certain skin diseases may result from treatment –Psoriasis from anti-TNF therapy –Squamous cell cancers

24. 24 Linda Next Steps Started on natalizumab No PG response Reversal of stoma considered