Prolonged Ileus As a Sole Manifestation Of

Int J Colorectal Dis (2004) 19:273Ð276 DOI 10.1007/s00384-003-0541-9 CASE REPORT

Eran Elinav Prolonged ileus as a sole manifestation David Planer Moshe E. Gatt of pseudomembranous enterocolitis

Accepted: 27 August 2003 Abstract Background: Pseudomem- tention rapidly worsened, requiring Published online: 15 November 2003 branous colitis usually manifests as an urgent subtotal colectomy. The © Springer-Verlag 2003 fever and diarrhea in hospitalized pa- macroscopic and microscopic ap- tients treated with systemic antibiot- pearance of the excised colon as well ics. We present a case that represents as results of the colonic cytotoxin es- a unique variant. Case presentation: say and fecal enzyme-linked immu- The 44-year-old man suffered of sev- nosorbent assay essay confirmed the eral weeks of abdominal pain, low- diagnosis of severe Clostridium diffi- grade fever, nausea, vomiting, and cile induced pseudomembranous co- lack of bowel movements. Upper litis as the cause of the patient’s ill- gastrointestinal barium swallow and ness. Conclusion: To our knowledge, passage series revealed evidence of this is the first reported case of Clos- severe intestinal hypomotility. A tridium-difficile induced disease E. Elinav (✉) á D. Planer á M. E. Gatt thorough evaluation for the cause of consisting of prolonged ileus in the Department of Medicine, the patient’s ileus and abdominal absence of diarrhea in a patient not Hadassah University Hospital, pain was unrevealing, and symptom- previously taking antibiotics. Mount Scopus, P.O. Box 24035, atic treatment was ineffective. Fol- 91240 Jerusalem, Israel e-mail: [email protected] lowing the administration of opiates Keywords Pseudomembranous Tel.: +972-2-5844520 and dietary fiber supplementation enterocolitis á Clostridium difficile á Fax: +972-2-5812754 the patient’s abdominal pain and dis- Ileus á Pseudo-obstruction

spinal magnetic resonance imaging studies, and an infectious, Introduction metabolic, autoimmune, and paraneoplastic workup, all yielding negative results. Five years earlier idiopathic recurrent deep vein Pseudomembranous colitis usually manifests as fever thrombosis of the calves had required the implantation of an infe- and diarrhea in hospitalized patients receiving systemic rior vena cava filter and the administration of chronic warfarin antibiotics. We present a case of Clostridium difficile treatment. The patient denied the use of any other prescribed, over-the-counter, natural medications and the abuse of illicit drugs induced disease in a patient not previously taking anti- and alcohol. biotics who had suffered prolonged ileus but without On admission the patient looked ill, with normal pulse rate, diarrhea. temperature, blood pressure, and arterial oxygen saturation. Physi- cal examination was notable for a mildly distended abdomen with diffusely hypoactive bowel sounds and for the previously known decreased sensation of the distal calves up to the level of the mid- Case report dle-ankle region. Laboratory tests, including complete blood count, renal and hepatic function tests, and erythrocyte sedimenta- A 44-year-old man patient was admitted for examination follow- tion rate were within normal values, while the international nor- ing 2 weeks of diffuse abdominal pain, nausea, vomiting, and con- malized ratio was 2.5 the reference levels due to chronic warfarin stipation. The patient noted no fever, diarrhea, or urinary symp- treatment. Abdominal computed tomography angiography at ad- toms. Significant past medical history included a painful, mainly mission showed an infrarenal inferior vena caval filter, with nor- sensory, nonprogressive peripheral polyneuropathy. It had been mal-looking, nondistended small and large bowels and patent me- thoroughly evaluated previously, with repeated lumbar punctures, senteric vessels. Evaluation during admission included infectious 274

cised colon and ileum showed severe pancolitis and ileitis, with pseudomembrane formation, deep mucosal ulceration, and an in- tense, mainly neutrophilic inflammatory exudate extending to all layers of the colon and ileum. Colonic Clostridium difficile cytotoxin essay was positive for the presence of C.difficile toxin A and B. Neither crypt abscesses in the intestinal wall nor vasculopathy, vasculitis, and thrombus formation in mesenteric arteries and veins were noted. The mesenteric nervous system showed no evidence of any pathological process such as inflammation, demye- linization, or axonal degeneration. Several stool samples taken shortly before surgery returned positive for C. difficile toxin A and B by enzyme-linked immunosorbent assay and were negative for the presence of Shigella, Salmonella, Campylobacter, and intestinal parasites. It was concluded that the patient’s prolonged ileus was a result of an atypical clinical variant of C. difficile infection, without a prior documented use of antibiotics and without diarrhea. The slowly progressive colitis was probably aggravated by the use of opiates and high fiber diet. Following a long rehabilitation process Fig. 1 Abdominal computed tomography section showing a se- the patient’s clinical condition gradually improved, and he finally verely thickened and edematous right (white arrows) and left regained regular bowel movements through his fully functioning (asterisk) colonic mucosa ileostomy. The abdominal pain, which has originally brought him to medical care, completely resolved. He is intended for ileocolic reimplantation in the near future. serologies, which were positive for remote infections with Ep- stein-Barr virus and cytomegalovirus and were negative for human Immunodeficiency virus, syphilis, and hepatitis A, B, and C virus- es. Blood, sputum, stool, and urine cultures for bacteria, Mycobac- Discussion terium, and funguses were repeatedly sterile. Autoimmune serolo- gy was negative for anti-nuclear factor, anti-phospholipid antibodies, cytoplasmatic and perinuclear anti-neutrophilic cytoplasmatic C. difficile infection is a common nosocomial disease, antibodies, and cryoglobulins, with normal levels of C3 and C4. usually caused by alteration of the normal intestinal flora No paraprotein was found in the patient’s serum or urine. Hemo- secondary to exposure to systemic antibiotics [1]. Clini- globin electrophoresis was negative for sickle cell disease and trait. There was no evidence of porphyrins in feces or blood. Vita- cally this infection causes a wide spectrum of illnesses, ranging from an asymptomatic carrier state [2, 3] and co- min B12 and B1 and folic acid levels were within the normal range, and repeated studies showed no evidence of a hypercoagulable litis with or without pseudomembrane formation [4] to disorder. Endoscopy and duodenal biopsy were normal. Upper life-threatening severe pancolitis [5, 6]. Treatment con- gastrointestinal barium swallow and passage series revealed se- sists of cessation of systemic antibiotics, antibiotic treat- vere intestinal hypomotility and were otherwise unremarkable. A nerve conduction study revealed a mild sensory polyneuropathy of ment with metronidazole or vancomycin, decompressive the distal calves, unchanged from a study performed a year earlier. colonoscopy, and, infrequently, emergency colectomy During the next 18 days the patient’s constipation, nausea, [7, 8]. vomiting, and several unexplained bouts of low-grade fever slow- Several rare clinical variants of C. difficile infection, ly progressed, unresponsive to nasogastric decompression, fluid replacement, cathartics, and promotility agents. On the 19th day described below, pose a great diagnostic challenge for he was given a therapeutic trial of high-fiber diet and mistakenly a the treating physicians. Due to their rarity their exact few courses of an opiate-containing antipain medication, shortly prevalence is currently unknown. after which he developed a marked aggravation of his abdominal Some reported patients suffer of C. difficile infection pain and distention, with concomitant worsening of his nausea and vomiting. Within a day his temperature increased to 39¡, pulse rate with fever and abdominal pain but with a total absence to 150 bpm, blood pressure dropped to 80/40, white blood cell of diarrhea. Infection in these patients usually leads to × 6 count increased to 15,000 10 , and pH and HCO3 dropping to 7.2 severe complications, including fulminant colitis and in- and 17 mmol/l, respectively. The patient was transferred to an intestinal perforations, most probably due to a delay in di- tensive care unit, intubated, aggressively hydrated, and put on a agnosis [9, 10]. C. difficile induced toxic megacolon is wide-spectrum antibiotic coverage of intravenous vancomycin, ceftazidime, and metronidazole. A repeated infectious workup was an extremely rare complication of severe pseudomem- negative. Plain abdominal radiography was notable for diffusely branous enterocolitis, manifesting as diffuse bowel dila- widened intestinal loops of bowel, while abdominal computed to- tation and systemic toxicity, often leading to life-threat- mography revealed evidence of severe diffuse mucosal thickening ening bowel perforation [11, 12]. of the entire colon and some of the small intestine, with patent mesenteric vessels, and no sign of colonic perforation or megacolon Patients suffering of inflammatory bowel disease (Fig. 1). (IBD) are more vulnerable to C. difficile induced disease Despite aggressive treatment the patient’s condition continued than the general population. In this group of patients to deteriorate rapidly, requiring an urgent exploratory laparotomy, pseudomembranous colitis may present as acute diarrhea which revealed inflammation of the entire colon and distal ileum, without evidence of perforation, abscess formation, or adhesions. imitating IBD exacerbation or even, more rarely, as the Subtotal colectomy and resection of the distal ileus was per- first bout of prolonged diarrhea in patients who are only formed, with ileostomy formation. Pathology results of the ex- later diagnosed as suffering from IBD. In either case 275

C. difficile infection is at times erroneously treated with cile being the only causative agent of his prolonged corticosteroids, aggravating the pseudomembranous coli- ileus. We believe that if it were not for the high fiber tis [13]. supplementation and opiate treatment given prior to our Other rare presentations of C. difficile infection in- patient’s final deterioration, his unexplained ileus would clude protein-losing enteropathy [14], intussusception in have lasted even longer before the correct diagnosis adults [15], colonic volvulus [16], chronic relapsing coli- reached. Earlier gastroenterological surgical consultation tis in young children leading to failure to thrive [17], and intervention may be appropriate in similar future colitis accompanied by extracolonic manifestations [18], cases. enteritis after proctocolectomy [19], colitis induced by A possible mechanism for this rare variant is the well- cancer chemotherapy [20], and pseudomembranous known in vitro inhibitory effect of C. difficile toxin B on colitis presenting as an acute abdomen [21]. One other spontaneous and carbachol-induced intestinal smooth reported patient has suffered of C. difficile infection pre- muscle activity [23]. In a rare susceptible patient C. diffi- senting as acute intestinal pseudo-obstruction without di- cile infection may cause a clinically significant toxin B arrhea [22]. In contrast to our reported patient, his pseu- mediated inhibition of colonic smooth muscle function, do-obstruction followed a recent antibiotic treatment for resulting in intestinal ileus and pseudo-obstruction. Our pneumonia, while his abdominal complaints only lasted patient’s peripheral polyneuropathy could have theoreti- 1 week. Conservative treatment including hydration, co- cally involved his mesenteric nervous system, making lonic decompression and treatment with intravenous him such a susceptible person. metronidazole resulted in his full recovery. Our patient is In conclusion, we suggest that C. difficile infection be the first documented case of C. difficile causing a pro- considered in the differential diagnosis of any patient longed (over 3 weeks) ileus in the absence of diarrhea, suffering of prolonged ileus, even in the absence of a pri- signs of toxic megacolon or acute abdomen, or a previ- or exposure to systemic antibiotics. This rare variant ous exposure to systemic antibiotics. Although our pa- should be added to the list of unusual manifestations of tient has previously suffered of several chronic illnesses, C. difficile infection. Until a larger, population-based including a hypercoagulation tendency and a mild senso- trial establishes the prevalence of this and other rare ry polyneuropathy, his repeated computed tomography variants, a high clinical index of suspicion is needed for angiography, intestinal pathology results, and positive the early recognition and treatment of this potentially C. difficile toxin essays are all in strong favor of C. diffi- life-threatening C. difficile infection.

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