Recurrent pneumonia and colobronchial fistula from Crohn’s disease: Infliximab alters and simplifies surgical management
Nuria Rosa Mercadal, Eric A. Wiebke
Indiana University School of Medicine, Indianapolis, USA
Department of Surgery, Indiana University School of Medicine, Indianapolis IN, USA
Conflict of Interest: None
Correspondence
to: Eric A. Wiebke, MD, MBA, Department of Surgery, 545 Barnhill Drive EH 509, Indianapolis IN, 46202 USA, Tel: +1-317 274 4990, Fax: +1-317 274 0241,
e-mail: ewiebke@iupui.edu
Received 30 March 2012; accepted 18 April 2012
Abstract
We report a rare case of right-sided colobronchial fistula in a 47-year-old, severely malnourished male with a history of regional enteritis and recurrent right lower and middle lobe pneumonias medically managed with the addition of the immunomodulator infliximab prior to surgery. On admission, evaluation of sputum cultures and chest radiograph pattern of pneumonia led to the suspicion of colobronchial fistula. This diagnosis was confirmed by abdominal CT enteroclysis. This patient’s pneumonia was initially treated with empiric antibiotics, then focused antibiotics based on culture results. The treatment for the regional enteritis and the secondary colobronchial fistula consisted of immunosuppression with infliximab, bowel rest, and total parenteral nutrition. The patient was discharged on a limited course of prednisone and received maintenance therapy with 3mg/kg IV infliximab infusions for four additional treatments with dramatic improvement in his clinical condition. Surgical therapy consisted of only bowel resection; no thoracic surgery or lung resection was necessary. The patient has had a dramatic improvement in his clinical condition and is currently disease-free on no maintenance therapy. The use of TNF-blocking agents such as infliximab may simplify the surgical approach in patients with complicated fistulous Crohn’s disease.
Keywords Crohn’s disease, infliximab, colobronchial fistula
Ann Gastroenterol 2012; 25 (4): 361-364
Introduction
Crohn’s disease is a chronic condition of unknown etiology with a North American prevalence of 26-199 per 100,000 individuals [1]. It is characterized by full thickness intramural inflammation of the gastrointestinal (GI) tract most commonly affecting the small bowel and colon. Complications, such as recurrence of enteric and enterocutaneous fistulas, are pathognomonic of this disease, and can occur in up to 50% of patients [2]. Fistulous disease commonly presents as enteroenteric, enterocolic, enterocutaneous, but perianal fistulas are most common [3]. Less common are gastrointestinal fistulas to the urinary tract. Since 1950, only eight cases of colobronchial fistulas, typically left-sided, a rare complication of Crohn’s disease, have been reported. We report a rare case of colobronchial fistula resulting in recurrent right-sided pneumonias in a young man with uncontrolled regional enteritis and the surgical management that led to successful long-term recovery.
Case report
After referral from a local hospital in late 2010, a 45-year-old male patient with history of Crohn’s disease and recurrent pneumonias for almost two years, presented with enterocutaneous abdominal fistula and one week of progressive pleuritic right chest pain radiating to the right shoulder, fever, and productive cough with foul smelling brownish sputum. He had a 30 pound weight loss. Past medical history included a twenty pack-year smoking history, five-year history of regional enteritis, and multiple operations including enterocutaneous fistula takedowns and right hemicolectomy in 2004.
Prior to admission, he reported symptoms of loose stools. The patient had failed to follow up with Gastroenterology for treatment of his regional enteritis and had not been adherent to an immunosuppressive therapy regimen.
On admission, vital signs were: temperature 38.3 °C, heart rate 84, blood pressure 116/76, and O2 saturation of 94%. He was cachectic. Pulmonary exam was notable for coarse rhonchi at the base of the right chest and mildly labored breathing. Pertinent laboratory data demonstrated WBC 3,700/dL, hemoglobin 9 g/dL, erythrocyte sedimentation rate 66 mm/h, and pre-albumin 9 mg/dL. Initial chest radiograph showed bilateral basilar airspace opacities worse on the right and blunting of the right costophrenic angle (Fig. 1). Bronchoscopy and sputum cultures grew polymicrobial enteric organisms and abdominal CT enterography was the diagnostic test that confirmed a right colobronchial fistula (Fig. 2) and also multiple other colonic fistulas. The duodenum and small bowel showed no evidence of mucosal distortion.
Initially, the pneumonia was treated with empiric antibiotics, and Crohn’s disease was treated with IV ciprofloxacin, metronidazole, bowel rest and total parenteral nutrition. Gastroenterology had previously recommended delaying infliximab until pneumonia was well controlled. He refused upper endoscopy and upper GI series was done showing normal gastric mucosa and confirming the normal duodenal findings of the CT enteroclysis. After antibiotics were started, we started immunosuppressive therapy with azathiprine and budesonide. He did not tolerate azathioprine. Infliximab (3 mg/kg) with acetaminophen premedication was initiated after five days of antibiotics. After discharge, outpatient maintenance therapy and remission of Crohn’s disease was attained with four-weekly infliximab infusions (3 mg/kg) for a total of five doses, prednisone (did not tolerate budesonide), and suppressive amoxicillin/clavulanate. Significant improvement was evident after a twenty pound weight gain, mild intermittent non-productive cough, no recurrence of fevers and malaise, and normalization of chest radiograph (Fig. 3). Antibiotics, and total parenteral nutrition (TPN) were stopped and steroids were weaned off.
Exploratory laparotomy revealed multiple colocolonic fistulas and a colonic fistula at the hepatic flexure that led into a sinus tract going up over the liver and to the diaphragm. The small bowel was normal as was the rectum and colon on flexible sigmoidoscopy to 40 cm. Total abdominal colectomy was performed with subsequent debridement of granulation tissue within the fistula tract. Surgery concluded with a side- to-side ileoproctostomy. No major complications developed in the post-operative period. Pathology of the resected colon revealed no active Crohn’s disease at either the proximal small bowel margin or the distal rectal margin. He remains non-compliant with follow-up and has failed to keep his gastroenterology appointments.
Discussion
Although colobronchial fistulas are a rare complication of Crohn’s disease, they should be highly suspected in patients with chronic respiratory symptoms and poorly controlled Crohn’s disease. Diagnostic tests to determine pneumonia secondary to enteric fistula should include a chest radiograph, bronchoscopy, and sputum cultures consistent with enteric organisms. In this case, suspected colobronchial fistula was confirmed by abdominal CT enterography, an excellent tool for imaging complex Crohn’s disease patients [4,5]. Half of the reported cases of visualized colobronchial fistulas used barium or gastrographin enema [6-9]; the remainder visualized them using abdominal CT [10-13]. The majority of fistulas are to the left chest, presumably because the liver protects the right diaphragm from the inflammatory process.
In all previous eight cases of colobronchial fistula, surgery was the standard of care and included bowel resection of the segment involved in the fistula trajectory and often diaphragmatic and pulmonary wedge resection [6-13]. One case did attempt, but failed, to close colobronchial fistula medically with one month of 6-mercapropurine [6]. In our case, because of the poor nutritional state and the severity of Crohn’s disease, medical management, to include TPN and infliximab, was our initial goal until optimal conditions for surgery were attained. Infliximab and other TNF-blocking agents have shown dramatic results in some patients with Crohn’s disease [14-16]. Infliximab appears to have great utility in unusual cases of fistulizing Crohn’s disease [17-19], although it does not replace surgery in most cases because of recurrence [20]. The current patient’s treatment with infliximab resulted in dramatic clinical improvement and likely changed the type of surgery required. Although the patient’s clinical course indicated possible healing of the colobronchial fistula, the additional multiple colocolonic fistulas required a surgical solution. Ultimately, a completion colectomy and debridement of the fistula were simplified by previous medical management with infliximab. No pulmonary, liver, or diaphragmatic resections were needed.
In conclusion, medical management with immunosuppressive therapy using infliximab is a successful pre-operative adjunct to surgical management for treatment of colobronchial fistula in patients with Crohn’s disease and recurrent pneumonia. The use of this class of TNF-blocking agents may simplify the surgical approach in patients with complicated fistulous Crohn’s disease.
References
1. Loftus EV, Jr, Schoenfeld P, Sandborn WJ. The epidemiology and natural history of Crohn’s disease in population-based patient cohorts from North America: a systematic review. Aliment Pharmacol Ther 2002;16:51-60.
2. Nielsen OH, Rogler G, Hahnloser D, Thomsen OO. Diagnosis and management of fistulizing Crohn’s disease. Nat Clin Pract Gastroenterol Hepatol 2009;6:92-106.
3. Schwartz DA, Loftus EV, Jr, Tremaine WJ, et al. The natural history of fistulizing Crohn’s disease in Olmsted County, Minnesota. Gastroenterology 2002;122:875-880.
4. Bruining DH, Siddiki HA, Fletcher JG, et al. Prevalence of penetrating disease and extraintestinal manifestations of Crohn’s disease detected with CT enterography. Inflamm Bowel Dis 2008;14:1701-1706.
5. Booya F, Akram S, Fletcher JG, et al. CT enterography and fistulizing Crohn’s disease: clinical benefit and radiographic findings. Abdom Imaging 2009;34:467-475.
6. Singh D, Cole JC, Cali RL, et al. Colobronchial fistula: an unusual complication of Crohn’s disease. Am J Gastroenterol 1994;89:2250-2252.
7. Karmy-Jones R, Chagpar A, Vallieres E, Hamilton S. Colobronchial fistula due to Crohn’s disease. Ann Thorac Surg 1995;60:446-448.
8. Domej W, Kullnig P, Petritsch W, et al. Colobronchial fistula: a rare complication of Crohn’s colitis. Am Rev Respir Dis 1990;142:1225-1227.
9. Flueckiger F, Kullnig P, Melzer G, Posch E. Colobronchial and gastrocolic fistulas: rare complication of Crohn’s disease. Gastrointest Radiol 1990;15:288-290.
10. Mera A, Sugimoto M, Fukuda K, et al. Crohn’s disease associated with colo-bronchial fistula. Intern Med 1996;35:957-960.
11. Lozano M, Toscano E, Moreno de la Santa P, et al. [Laparoscopic resection of a colobronchial fistula in a patient with Crohn’s disease; a rare complication treated using a new approach]. Cir Esp 2009;85:57-58.
12. Badiani S, Bowley D, Steyn R, et al. A very ‘tickly’ cough. Colorectal Dis 2011;13:e87-e89.
13. Alameel T, Maclean DA, Macdougall R. Colobronchial fistula presenting with persistent pneumonia in a patient with Crohn’s disease: a case report. Cases J 2009;2:9114.
14. Present DH, Rutgeerts P, Targan S, et al. Infliximab for the treatment of fistulas in patients with Crohn’s disease. N Engl J Med 1999;340:1398-1405.
15. Sands BE, Anderson FH, Bernstein CN, et al. Infliximab maintenance therapy for fistulizing Crohn’s disease. N Engl J Med 2004;350:876-885.
16. Colombel JF, Schwartz DA, Sandborn WJ, et al. Adalimumab for the treatment of fistulas in patients with Crohn’s disease. Gut 2009;58:940-948.
17. Sands BE, Blank MA, Patel K, van Deventer SJ. Long-term treatment of rectovaginal fistulas in Crohn’s disease: response to infliximab in the ACCENT II Study. Clin Gastroenterol Hepatol 2004;2:912-920.
18. Nunes J, Santos PM, Tavares L. Complete resolution of enterocolic fistulas with infliximab. BioDrugs 2010;24(Suppl 1):28-30.
19. Uza N, Nakase H, Ueno S, et al. The effect of medical treatment on patients with fistulizing Crohn’s disease: a retrospective study. Intern Med 2008;47:193-199.
20. Poritz LS, Rowe WA, Koltun WA. Remicade does not abolish the need for surgery in fistulizing Crohn’s disease. Dis Colon Rectum 2002;45:771-775.