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Disseminated mycobacterial infection mimicking erythema nodosum in a patient with Crohn’s Disease on infliximab therapy
AJG – September, Suppl., 2002
related side effects of this formulation compared with conventional steroids. aCampieri, et al. Gut. 1997;41:209 –14; bD’Haens, et al. Aliment Pharmacol Ther. 1998;12:419 –24. 800 DISSEMINATED MYCOBACTERIAL INFECTION MIMICKING ERYTHEMA NODOSUM IN A PATIENT WITH CROHN’S DISEASE ON INFLIXIMAB THERAPY Emily L. Cooper, M.D., David Patterson, M.D.* and Robert Rakita, M.D. Gastroenterology, Virginia Mason Medical Center, Seattle, WA. Introduction: Infliximab, a TNF–alpha antibody increases the risk of opportunistic infections. We present a case of disseminated Mycobacterium chelonae infection in a woman receiving infliximab for Crohn’s. Case Presentation: A 36 –year– old woman with a 22–year history of Crohn’s presented with a protracted course of arthralgias and skin lesions consistent with erythema nodosum. She underwent repeated infliximab infusions and total proctocolectomy with ileostomy with failure to resolve her skin lesions. She developed right index finger pain and swelling. Her medications included prednisone, infliximab (received 4 weeks prior), and three Solumedrol injections to the PIP joint. On physical examination she was afebrile with stable vital signs. She had a cushingoid appearance. A left tunneled subclavian catheter site was intact. Her right index finger was warm, erythematous and edematous at the PIP joint. She had greater than fifty erythematous nodules, some with a violaceous appearance, on her legs and arms. Two additional small lesions were present on her face. Several lesions on the lower extremities were open and draining. Radiographic films revealed bony destruction of the distal end of the proximal phalanx consistent with osteomyelitis. An operative incision and drainage with removal of the proximal phalanx was performed. Skin and bone biopsies revealed rapid growing acid–fast bacilli, later identified as Mycobacterium chelonae. Blood cultures from the central line were positive as well. Initially she received clarithromycin, amikacin, and cefoxitin. Her skin lesions began to resolve and she was discharged home. After definitive identification, amikacin and cefoxitin were discontinued. At six weeks post– hospitalization, she continues to improve on clarithromycin therapy. Discussion: Infliximab therapy causes immunosuppression and as its use increases more cases of atypical infections are being reported. There have been ten, as yet unsubstantiated, reports of atypical mycobacterial infections associated with infliximab. Eight cases were in patients with rheumatoid arthritis, one in a patient with juvenile rheumatoid arthritis, and one unknown. An association with Mycobacterium chelonae and line infections has previously been reported. We present the first reported case of disseminated Mycobacterium chelonae in a patient on infliximab therapy for Crohn’s disease. 801 COMPARABLE SYSTEMIC ABSORPTION OF 5–ASA AND N– AC–5–ASA FROM U.S. ASACOL AND COLAZAL William J. Sandborn, M.D.*, Stephen B. Hanauer, M.D. and Akshay B. Buch, Ph.D. Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN; Division of Gastroenterology, University of Chicago, Chicago, Il and Clinical Pharmacology and Pharmacokinetics, Procter & Gamble Pharmaceuticals, Mason, OH. Purpose: To compare the pharmacokinetics (PK) of 5–ASA and N–Ac– 5–ASA from equimolar mesalamine doses of U.S. Asacol威 (mesalamine) delayed–release tablets and Colazal威 (balsalazide disodium) capsules in healthy male and female volunteers. Methods: A total of 19 subjects (12 males and 7 females, age range 19 to 41 years) completed this open–label, two period, randomized crossover study. After an overnight fast, subjects received single doses of 800 mg of 5–ASA, either as 2X400 mg Asacol tablets or 3X750 mg Colazal capsules. These doses represent labeled doses for treatment of mildly to moderately active ulcerative colitis. For each subject, over a period of 72 hours after each dose, 15 plasma and 8 urine samples were collected and analyzed for
Abstracts
S263
5–ASA and N–Ac–5–ASA using validated liquid chromatography and mass spectrometry assays. Pharmacokinetic parameters were calculated using non– compartmental methods. Safety was monitored by evaluating adverse events. Results: Asacol and Colazal both exhibited a delayed release profile with a median lag time (tlag) of 5–ASA of 4 hr and 3 hr, respectively. The pharmacokinetic parameters for Asacol and Colazal are shown in the following table:
5–ASA
N–Ac–5–ASA
Geometric Means Geometric Means (Nⴝ19) (Nⴝ19) Pharmacokinetic Parameter Asacol Colazal p–value Asacol Colazal p–value Cmax (ng/mL) AUC (tlast) (ng hr/mL) %Dose in urine
319 3295
348 3449
0.80 0.85
927 15364
1009 16190
0.67 0.64
0.39
0.37
0.78
18.8
18.9
0.97
The total (5–ASA and N–Ac–5–ASA) urinary excretion was 19.26% and 19.35% for Asacol and Colazal, respectively (p⫽0.97). Both products were well tolerated by the subjects and there were no clinically significant adverse events reported during the study.
Conclusions: Results indicate that systemic absorption of 5–ASA and N–Ac–5–ASA from U.S. Asacol and Colazal are comparable based upon plasma PK parameters and urinary excretion data.
802 COMPARISON OF WIRELESS CAPSULE ENDOSCOPY (CE), ILEOSCOPY AND SMALL BOWEL FOLLOW THROUGH (SBFT) FOR THE EVALUATION OF NON–STRICTURING IBD Marc D. Rosenberg, M.D., Yvonne Miller–Griffin, Steven Klein, M.D., Todd Fibus and Peter D. Bloom, M.D.*. Division of Digestive Diseases, Emory University School of Medicine, Atlanta, GA and Gastroenterology Section, Atlanta VA Medical Center, Decatur, GA. Purpose: To compare CE of the small intestine (SI) in patients with known or suspected non–stricturing Crohn’s disease to conventional techniques for the evaluation of the SI in patients with IBD (colonoscopy with ileoscopy and SBFT). Methods: Retrospective comparison of CE (Given Imaging M2A™ capsule) to ileoscopy and SBFT findings among 11 patients with known or suspected non–stricturing Crohn’s disease. Ileoscopy and SBFT were performed prior to CE to exclude overt asymptomatic strictures. Results: See Table 1. Table 1 Comparison of Capsule Endoscopy, Ileoscopy and SBFT Findings
Patient #
Ileoscopy
SBFT
Capsule Endoscopy normal aphthoid ulcerations throughout small bowel normal poor prep, inconclusive aphthoid ulceration TI aphthoid ulceration TI normal normal normal normal normal
1. 2.
normal aphthoid ulceration TI
normal normal
3. 4. 5. 6. 7. 8. 9. 10. 11.
normal normal aphthoid ulceration TI aphthoid ulceration TI normal normal normal normal normal
normal normal normal normal normal normal normal normal normal
TI ⫽ terminal ileum
One patient had a poor prep limiting interpretation of mucosal lesions by CE. Findings suggestive of IBD were detected in 3/11(27.3%) patients by CE and ileoscopy with 100% correlation. SBFT failed to detect any lesion
related side effects of this formulation compared with conventional steroids. aCampieri, et al. Gut. 1997;41:209 –14; bD’Haens, et al. Aliment Pharmacol Ther. 1998;12:419 –24. 800 DISSEMINATED MYCOBACTERIAL INFECTION MIMICKING ERYTHEMA NODOSUM IN A PATIENT WITH CROHN’S DISEASE ON INFLIXIMAB THERAPY Emily L. Cooper, M.D., David Patterson, M.D.* and Robert Rakita, M.D. Gastroenterology, Virginia Mason Medical Center, Seattle, WA. Introduction: Infliximab, a TNF–alpha antibody increases the risk of opportunistic infections. We present a case of disseminated Mycobacterium chelonae infection in a woman receiving infliximab for Crohn’s. Case Presentation: A 36 –year– old woman with a 22–year history of Crohn’s presented with a protracted course of arthralgias and skin lesions consistent with erythema nodosum. She underwent repeated infliximab infusions and total proctocolectomy with ileostomy with failure to resolve her skin lesions. She developed right index finger pain and swelling. Her medications included prednisone, infliximab (received 4 weeks prior), and three Solumedrol injections to the PIP joint. On physical examination she was afebrile with stable vital signs. She had a cushingoid appearance. A left tunneled subclavian catheter site was intact. Her right index finger was warm, erythematous and edematous at the PIP joint. She had greater than fifty erythematous nodules, some with a violaceous appearance, on her legs and arms. Two additional small lesions were present on her face. Several lesions on the lower extremities were open and draining. Radiographic films revealed bony destruction of the distal end of the proximal phalanx consistent with osteomyelitis. An operative incision and drainage with removal of the proximal phalanx was performed. Skin and bone biopsies revealed rapid growing acid–fast bacilli, later identified as Mycobacterium chelonae. Blood cultures from the central line were positive as well. Initially she received clarithromycin, amikacin, and cefoxitin. Her skin lesions began to resolve and she was discharged home. After definitive identification, amikacin and cefoxitin were discontinued. At six weeks post– hospitalization, she continues to improve on clarithromycin therapy. Discussion: Infliximab therapy causes immunosuppression and as its use increases more cases of atypical infections are being reported. There have been ten, as yet unsubstantiated, reports of atypical mycobacterial infections associated with infliximab. Eight cases were in patients with rheumatoid arthritis, one in a patient with juvenile rheumatoid arthritis, and one unknown. An association with Mycobacterium chelonae and line infections has previously been reported. We present the first reported case of disseminated Mycobacterium chelonae in a patient on infliximab therapy for Crohn’s disease. 801 COMPARABLE SYSTEMIC ABSORPTION OF 5–ASA AND N– AC–5–ASA FROM U.S. ASACOL AND COLAZAL William J. Sandborn, M.D.*, Stephen B. Hanauer, M.D. and Akshay B. Buch, Ph.D. Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN; Division of Gastroenterology, University of Chicago, Chicago, Il and Clinical Pharmacology and Pharmacokinetics, Procter & Gamble Pharmaceuticals, Mason, OH. Purpose: To compare the pharmacokinetics (PK) of 5–ASA and N–Ac– 5–ASA from equimolar mesalamine doses of U.S. Asacol威 (mesalamine) delayed–release tablets and Colazal威 (balsalazide disodium) capsules in healthy male and female volunteers. Methods: A total of 19 subjects (12 males and 7 females, age range 19 to 41 years) completed this open–label, two period, randomized crossover study. After an overnight fast, subjects received single doses of 800 mg of 5–ASA, either as 2X400 mg Asacol tablets or 3X750 mg Colazal capsules. These doses represent labeled doses for treatment of mildly to moderately active ulcerative colitis. For each subject, over a period of 72 hours after each dose, 15 plasma and 8 urine samples were collected and analyzed for
Abstracts
S263
5–ASA and N–Ac–5–ASA using validated liquid chromatography and mass spectrometry assays. Pharmacokinetic parameters were calculated using non– compartmental methods. Safety was monitored by evaluating adverse events. Results: Asacol and Colazal both exhibited a delayed release profile with a median lag time (tlag) of 5–ASA of 4 hr and 3 hr, respectively. The pharmacokinetic parameters for Asacol and Colazal are shown in the following table:
5–ASA
N–Ac–5–ASA
Geometric Means Geometric Means (Nⴝ19) (Nⴝ19) Pharmacokinetic Parameter Asacol Colazal p–value Asacol Colazal p–value Cmax (ng/mL) AUC (tlast) (ng hr/mL) %Dose in urine
319 3295
348 3449
0.80 0.85
927 15364
1009 16190
0.67 0.64
0.39
0.37
0.78
18.8
18.9
0.97
The total (5–ASA and N–Ac–5–ASA) urinary excretion was 19.26% and 19.35% for Asacol and Colazal, respectively (p⫽0.97). Both products were well tolerated by the subjects and there were no clinically significant adverse events reported during the study.
Conclusions: Results indicate that systemic absorption of 5–ASA and N–Ac–5–ASA from U.S. Asacol and Colazal are comparable based upon plasma PK parameters and urinary excretion data.
802 COMPARISON OF WIRELESS CAPSULE ENDOSCOPY (CE), ILEOSCOPY AND SMALL BOWEL FOLLOW THROUGH (SBFT) FOR THE EVALUATION OF NON–STRICTURING IBD Marc D. Rosenberg, M.D., Yvonne Miller–Griffin, Steven Klein, M.D., Todd Fibus and Peter D. Bloom, M.D.*. Division of Digestive Diseases, Emory University School of Medicine, Atlanta, GA and Gastroenterology Section, Atlanta VA Medical Center, Decatur, GA. Purpose: To compare CE of the small intestine (SI) in patients with known or suspected non–stricturing Crohn’s disease to conventional techniques for the evaluation of the SI in patients with IBD (colonoscopy with ileoscopy and SBFT). Methods: Retrospective comparison of CE (Given Imaging M2A™ capsule) to ileoscopy and SBFT findings among 11 patients with known or suspected non–stricturing Crohn’s disease. Ileoscopy and SBFT were performed prior to CE to exclude overt asymptomatic strictures. Results: See Table 1. Table 1 Comparison of Capsule Endoscopy, Ileoscopy and SBFT Findings
Patient #
Ileoscopy
SBFT
Capsule Endoscopy normal aphthoid ulcerations throughout small bowel normal poor prep, inconclusive aphthoid ulceration TI aphthoid ulceration TI normal normal normal normal normal
1. 2.
normal aphthoid ulceration TI
normal normal
3. 4. 5. 6. 7. 8. 9. 10. 11.
normal normal aphthoid ulceration TI aphthoid ulceration TI normal normal normal normal normal
normal normal normal normal normal normal normal normal normal
TI ⫽ terminal ileum
One patient had a poor prep limiting interpretation of mucosal lesions by CE. Findings suggestive of IBD were detected in 3/11(27.3%) patients by CE and ileoscopy with 100% correlation. SBFT failed to detect any lesion