A 24-year-old male from Saudi Arabia with CMMRD syndrome was referred to our clinic for further evaluation of his abdominal pain and high stoma output one year after duodenal segmental resection (D4), for adenocarcinoma.
In this patient, CMMRD was caused by a biallelic PMS2 mutation, which led to the development of acute lymphoblastic leukemia at age 3, colorectal cancer (two synchronous lesions) at age 19, and duodenal adenocarcinoma at age 22 years. He had completed multiple courses of chemotherapy throughout his lifetime: POG protocol 9006 with ara-C, prednisone and asparaginase at age 3 for the acute lymphoblastic leukemia, and at age 19 adjuvant mFOLFOX for the colorectal cancer. He had undergone total colectomy with end ileostomy at age 19 for the colorectal cancer. Notably, the patient's parents were first cousins.
Two months before being seen in the clinic, he developed abdominal pain, an 8-kg unintentional weight loss, intermittent nausea and vomiting, and increased stoma output. The patient denied taking non-steroidal anti-inflammatory drugs. Examination revealed a young man of ill appearance weighing 34 kg (body mass index: 14.7 kg/m2). His abdomen was tender to palpation near the ileostomy site. There were multiple 5-10 mm hypopigmented macules on the trunk and extremities.
Further laboratory investigations revealed the presence of mild microcytic anemia (Hb 10.9 g/dL [ref. range: 11.1-15.9 g/dL], MCV 74.9 fL [ref. range: 79-97 fL]), thrombocytosis (550 K/cu mm [ref. range: 150-350 K/cu mm]), elevated fecal calprotectin (464 mcg/g [ref. range <162.9 mcg/g]) and C-reactive protein (2.7 mg/L [ref. range <0.5mg/L]). QuantiFERON and stool specimens were negative for tuberculosis, bacterial or parasitic infections (including Clostridium difficile). During ileoscopy we noted patchy erythema and ulcers in the terminal ileum; however, the pathology was consistent with nonspecific acute enteritis. There was no histological evidence of vasculitis, ischemia or cytomegalovirus infection. No granulomata were seen. The patient was treated conservatively for partial small bowel obstruction, and discharged on budesonide and mesalamine for suspicion of emerging Crohn's disease.
Two months later, the patient noticed only a minimal improvement of symptoms, despite an increase in the prednisone dose (40 mg daily). Repeat endoscopy showed increased friability of the mucosa, with superficial ulcerations and a dilated ileum with narrowing at the ileostomy. Histological evidence of acute ileitis was present (Fig. 1), but again there were no signs of chronicity. The patient had ostomy revision as his symptoms were likely to be due to partial bowel obstruction (secondary to adhesions) rather than Crohn's disease.
Two months after surgery, symptoms reoccurred. Repeat endoscopy (Fig. 2) revealed mucosal edema and erythema with several aphthoid ulcers. The pathology (Fig. 3) was consistent with chronic ileitis, including pyloric gland metaplasia and moderate crypt distortion, highly suggestive of Crohn's disease.
The findings from the third endoscopy, in combination with the aforementioned histologic findings, as well as the patient's presentation and progression during follow up, led to the final diagnosis of Crohn's disease.
The choice of therapy was complicated by the high underlying risk of malignancy in this patient. Vedolizumab was the drug of choice because of its safety profile. The patient responded well, achieving clinical and endoscopic remission by week 12. Unfortunately, several months later, surveillance endoscopy revealed jejunal adenocarcinoma, and vedolizumab therapy (6-month therapy duration; 6 infusions total, including induction) was stopped in preparation for surgery. Presently, the patient is recovering well, with ileoscopy scheduled 3 months postoperatively to re-stage his condition. He will continue to undergo surveillance enteroscopy every 6 months.