Extraintestinal Manifestations of IBD Case Studies William Tremaine, M.D. Case 1 History 18 year-old woman with Crohn s disease Onset at age 5: colonic & perianal Sulfasalazine, prednisone, mercaptopurine Long strictures: rectum and transverse colon Age 16 Proctocolectomy with ileostomy Age 17 Peristomal pyoderma gangrenosum CP123456-0 1
Case 1 History (continued) Age 18 Worsening pyoderma despite: Mercaptopurine, Infliximab Hughes AP. JAMA 2000;284:1546-1548 2
Peristomal Pyoderma Gangrenosum Peristomal Pyoderma Gangrenosum Treatment options? 3
Conditions Associated with PG Crohn s disease Ulcerative colitis Chronic hepatitis Rheumatoid arthritis AML and CML Polycythemia vera Myeloma 30% to 50% may be idiopathic Demographics of PPG UC Crohn's Diverticulitis Adenoca Neurogenic Bladder Perforated bowel Lyon et al. J Am Acad Dermatol 2000:42:992 4
Demographics of PPG Annual incidence estimated at 0.6 per 100 ostomies 1 Time to onset after surgery 2 months to 25 years 2 1 Lyon et al. J Am Acad Dermatol 2000:42:992 Diagnosis of PPG Inflammatory disease in most Painful pink/purple papule Painful ulceration Raised purple edge Strands of persisting epidermis stretch across the ulcer Involves the area covered by the stoma bag adhesive plate 2 Hughes AP et al. JAMA 2000:284:1546 Lyon et al. J Am Acad Dermatol 2000:42:992 5
Diagnosis of PG: Rule out other causes of persistent ulcers Vascular occlusive or venous disease Antiphospholipid antibody syndrome Vasculitis Wegner s granulomatosis, Polyarteritis nodosum Lymphoma Deep fungal infection Exogenous tissue injury Munchausen s syndrome Cutaneous Crohn s disease Weenig et al. N Eng J Med 2002:347:1412 Common Misdiagnoses in PPG Stitch abscess Contact dermatitis Irritation from leakage of feces or urine Extension of underlying Crohn s disease Wound infection Hughes AP et al. JAMA 2000:284:1546 6
Diagnostic Tests Rule out other conditions Laboratory investigations None are pathognomonic Protein electrophoresis, CBC, coagulation panel, antiphospholipid antibody panel, cryoglobulins, vasculitis screen Biopsy No pathognomonic characteristics 46 of 86 (53%) of misdiagnosed patients in Mayo series had correct diagnosis evident on biopsy Therapy of PPG Current knowledge of therapy based on case series No RCTs Observational studies uniformly lack a control group Weenig et al. N Eng J Med 2002:347:1412 7
Systemic Agents Reported Possibly Effective in PG Corticosteroids Minocycline Dapsone Cyclosporine Tacrolimus Clofazamine Cyclophosphamide Melphalan Chlorambucil Powel et al. Dermatol Clin 2002:20:347 Azathioprine Methotrexate Interferon-α Potassium iodide Thalidomide Infliximab Adalimumab Mycophenolate mofetil Colchicine Medications for Severe PG Tacrolimus Cyclosporine Infliximab Cyclophosphamide Poritz LS. J Am Coll Surg 2008; 206: 311-5 Alkhouri N. Inflam Bowel Dis 2009. 15(6): 803-5 8
Topical Tacrolimus for PPG Topical tacrolimus - 7 of 11 healed in mean 5.1 weeks vs. Topical steroids - 5 of 13 healed in mean 6.5 weeks Topical tacrolimus superior for large lesions (> 2cm in diameter) Lyon CC et al. J Dermatol Treatment 2001;12:13 IV Cyclosporine Mt Sinai 11 patients with steroid-refractory PG All healed with IV CSA followed by oral CSA Mean time to response 4.5 days Mean time to healed 1.4 months 9 of 11 discontinued steroids and were maintained on AZA/6-MP Friedman S et al. Inflammatory Bowel Disease 2001;7:1 9
Anti-TNFα Therapy for PG Relatively few reports Eight patients with PG and active CD 3 patients with complete healing and maintenance of healing 3 patients with partial healing or complete healing but relapse and intolerance to infliximab 2 patients without healing Response may depend on healing underlying CD but insufficient data to know for certain Ljung T et al. Scand J Gastroenterol 2002:37:1108 Cyclophosphamide for PG First reported in 1967 Pulse Cyclophosphamide first reported in 1994 Rapid healing and prolonged improvement in 2 patients with RA Additional data needed given recent evidence of effectiveness in CD Crawford SE et al. J pediatrics 1967:71:255 Zonana-Nacach A et al. J Rheumatol 1994:21:1352 10
Peristomal Pyoderma Summary Rule out other diagnoses Initial therapy with topical corticosteroids for small lesions and high dose corticosteroids or topical tacrolimus for large lesions Second line therapies include CSA, TAC, topical TAC, infliximab, other immunomodifiers, dapsone Comparative trials of therapies greatly needed Dermatological Manifestations Pyoderma gangrenosum 1-10% Erythema nodosum 1-10% Cutaneous Crohn s disease (rare) Psoriasis (up to 10%) Uncommon disorders Sweet s syndrome Epidermolysis bullosa acquisita 11
Erythema Nodosum More common in Crohn s (up to 15%), less in UC (up to 5%) Young women at most risk Painful tender erythematous nodules: pretibial, or areas of trauma Correlates with IBD activity Treat underlying IBD SKIN LESIONS Erythema Nodosum 12
Cutaneous Crohn s Disease Granulomatous lesions of skin Most common in perianal areas (e.g. tags) Metastatic Crohn s May not correlate with disease activity Steroids, immunosuppressives Case 2 Corneal Erosions 24 year old man Crohn s disease since age 18 Ileocolonic and perianal involvement Adalimumab weekly Nocturnal corneal erosions, recurrent Awakens with eye pain, dryness Rx: punctal plugs. Fell out. 13
Case 2 Corneal Erosions Case 2 Corneal Erosions (continued) Rx: punctal cautery, bilateral Still nocturnal awakening with burning eyes vaporizer, ointment, tetracaine Repeat trips to the ER for eye pain Stromal puncture, left eye 23-gauge needle, 200 corneal nicks Polytrim solution and erythromycin ointment: improved Right eye treatment: improved 14
Ocular Complications: Uveitis Inflammation of anterior chamber Prevalence 5% Ocular pain, redness, photophobia Slit lamp exam necessary for diagnosis Acute form associated with HLA B27 Chronic form not associated Treatment: Topical steroids, cycloplegic agents Oral steroids for refractory cases Immunosuppressives and anti-tnf agents Anterior Uveitis 15
Other Ocular Complications Episcleritis Episcleritis Outer layers of eye Eye burning or itching, erythema Activity correlates to IBD activity Topical corticosteroids Scleritis: more serious, oral steroids Retinitis: less common Cataracts, glaucoma due to steroids 16