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Paper text:
hirschsprung 's disease ( hd ) is a motor disorder of the gastrointestinal tract that is caused by a failure of neural crest cell migration during intestinal development .
the incidence of hd is approximately one in 5,000 live births,1 and the main treatment is surgical resection of the affected segment .
most patients experience normal or near - normal bowel function after definitive surgery for hd .
one complication of surgery for hd is enterocolitis , which presents as watery , bloody diarrhea combined with abdominal distension.2 cd is the generic name for a group of multisystem disorders with specific clinicopathological features , including focal , asymmetric , transmural , and occasionally granulomatous inflammation primarily affecting the gastrointestinal tract . ankylosing spondylitis ( as ) is common forms of chronic inflammatory arthritis and the archetypal spondyloarthritis.3 the clinical signs of as include sacroiliitis , inflammatory back pain , morning stiffness , acute anterior uveitis , and ibd .
between 5% and 10% of as cases are associated with ibd and either cd or uc.3 a study into the comorbidities of ibd showed that uc alone , and not cd , is associated with hd.4 in fact , cd comorbid with hd is extremely rare  to our knowledge , only two cases have been reported in the medical literature to date,56 and hd combined with both cd and as has never been described . in this report , we describe the case of a patient who had undergone surgery for hd as an infant , and was later diagnosed with cd combined with as .
a 17-year - old boy was referred from a secondary medical center to our gastrointestinal center because of chronic abdominal pain and diarrhea that had persisted for several years .
watery diarrhea occurred four times a day and was associated every other day with dull pain in the lower abdomen .
he had been diagnosed with hd and undergone ileostomy at the age of 4 months ; this was followed by a subtotal colectomy at 12 months of age , where surgeons used the lester martin modification of the duhamel procedure . since the age of 5 years
, he had been repeatedly hospitalized for postoperative enterocolitis ; he also had a history of uveitis , and had suffered from visual disturbance in the right eye since the age of 15 years .
he had been experiencing recurring aggravation of pain in the left ankle and knee , as well as in the back , until about 3 years prior to his visiting our center .
the patient was 167 cm tall and weighed 50 kg ( bmi , 17.92 ) . upon admission , his vital signs were blood pressure , 110/70 mmhg ; pulse rate , 72 beats per minute ; respiratory rate , 20 breaths per minute ; body temperature , 36.4. he appeared chronically ill , with pale conjunctivae .
abdominal examination revealed increased bowel sounds and tenderness in the lower abdomen , although no rebound tenderness or palpable abdominal masses were found , and rectal examination revealed no perianal disease .
slight edema and tenderness were observed in the left ankle and knee . a routine complete blood count detected hypochromic , microcytic anemia , as well as thrombocytosis  white blood cell count , 6.13010/l ; hemoglobin level , 5.5 g / dl ( mean corpuscular volume , 54.4 fl ; mean cell hemoglobin , 21.4 pg ) ; platelet count , 58710/l .
further laboratory tests revealed the following abnormalities  iron , 30 g / dl ; total iron - binding capacity , 394 g / dl ; ferritin , 16.12 ng / ml ; c - reactive protein level , 3.36 mg / dl .
no clostridium difficile toxin a was detected in a stool sample , and stool culture and parasite tests were negative .
enhanced ct of the abdomen and pelvis revealed a thickened wall in the small bowel ( neorectosigmoid junction , neosigmoid colon , and neoascending colon ) .
1 ) . colonoscopy revealed a normal rectal mucosa , but edematous mucosa and superficial ulcerations were observed above 10 cm from the anal verge . in fact , we were unable to advance the endoscope beyond 15 cm from the anal verge , because the intestinal lumen was so narrowed ( fig .
2 ) . a small bowel series revealed narrowing and streaky mucosal changes in the proximal small bowel and at the site of anastomosis , as well as multifocal stricture in the small bowel ( especially the neoascending colon and neosigmoid colon ) and around the site of anastomosis , with marked luminal dilatation consistent with cd ( fig .
3 ) . on the basis of these endoscopic and imaging findings , as well as his symptoms ,
while the diagnosis was being made , the patient 's uveitis worsened , as did his ankle and knee arthritis , and his back pain .
human leukocyte antigen b27 was detected in serum , and mri of the pelvis revealed sacroiliitis .
subsequently , we injected intravenous steroids and metronidazole ; to treat the cd combined with as , a course of infliximab injection was started .
the patient 's abdominal pain and diarrhea improved during hospitalization , and he was discharged on admission day 12 .
the mucosal edema and ulcerations that had been observed above 10 cm from the anal verge had improved , but small bowel evaluation was limited by an acute luminal angle .
the patient is currently within a 64-month observation period at dong - a university hospital .
he has tolerable gastrointestinal symptoms , but is being administered infliximab injections to treat uveitis .
hd is characterized by the congenital absence of ganglion cells in both the submucosal ( meissner 's ) and myenteric ( auerbach 's ) plexuses ; the disease is caused by a failure of neural crest cell ( enteric ganglion cell precursors ) migration during intestinal development .
the resulting aganglionic segment of the colon is unable to relax , leading to a functional obstruction .
many children with hd improve after surgical treatment ; nonetheless , long - term follow - up studies have identified a number of concerns .
indeed , hirschsprung - associated enterocolitis is a major cause of postoperative morbidity and occasional mortality.7 this complication occurs after the definitive pull - through procedure at a frequency of 30% to 40% , usually between 3 weeks and 20 months after surgery.289 occasionally , hirschsprung - associated enterocolitis needs to be differentiated from ibd or infectious enterocolitis .
the disease is diagnosed on the basis of the clinical findings ( detailed history , physical examination , endoscopy , histology , radiology , and laboratory investigations).10 however , it remains challenging to differentiate cd from other disorders such as acute infectious colitis , intestinal tuberculosis , uc , and behet 's colitis .
in particular , the postoperative state of hd mimics that of enterocolitis . both conditions present with diarrhea , hematochezia , fever , abdominal pain , and distension . however ,
postoperative hd can be distinguished from postoperative enterocolitis based on the former 's recurrent gastrointestinal symptoms , extraintestinal manifestations , radiological findings ( small bowel stricture , fistula , etc . ) , onset time , perianal disease , and therapeutic response to immunosuppression .
the association between as and human leukocyte antigen b27 is weaker in ibd - related as than in idiopathic as , and there is evidence of an association between as - related gut inflammation and cd - related card15 mutations.3 currently , infliximab is the drug of choice to treat patients with active as associated with ibd.3 in our patient , cd and as were diagnosed 16 years after hd , although he had repeatedly been hospitalized  up to five or six times a year  for recurrent diarrhea and abdominal pain . at each hospitalization , he had been diagnosed with enterocolitis and treated using antibiotics and supportive care .
subsequently , because of his recurring symptoms , severe anemia , and extraintestinal manifestations ( back pain , arthritis , and uveitis)which had persisted for several years  the patient was transferred to our hospital .
he was then diagnosed with cd combined with as on the basis of endoscopic , laboratory , radiographic , and mri findings .
thus , in patients who have undergone surgery to treat hd , and who present with recurrent diarrhea , abdominal pain with anemia , and extraintestinal manifestations , cd should be considered . in so doing , clinicians will avoid delayed cd diagnosis .
the immunological features common to hd and cd include increased expression of the major histocompatibility complex ii and intercellular adhesion molecule i antigens.111213 although each disease is associated with specific chromosomal disorders , none of these is common to both conditions.1415 moreover , no association between hd and cd has been previously reported .
however , we would suggest that our patient has a genetic mutation that makes him susceptible to cd and contributes to infections by multiple pathogens ( e.g. , salmonella spp .
campylobacter spp . , and c. difficile ) that are more frequent than in patients who have not undergone surgery .
these recurrent infections may have induced cd by triggering an inflammatory response that could not be controlled by the mucosal immune system .
further study on the association between cd and hd can provide a better understanding of the pathophysiology of cd . in summary
, cd occurs very rarely after surgery for hd , and diagnosis of the condition is challenging .
although postoperative enterocolitis is more common in patients with hd , cd should be considered in those who ( 1 ) present with multiple episodes of enterocolitis over a long time period ( 12 years ) after a definitive pull - through procedure and ( 2 ) have atypical symptoms such as arthritis , uveitis , and erythema nodosum .
crohn 's disease ( cd ) is a chronic , idiopathic , inflammatory disorder of the gastrointestinal tract . in rare cases , 
 cd has been associated with hirschsprung 's disease ( hd ) ; however , the underlying pathophysiology of this and other comorbidities is not yet fully understood . in this report 
 , we describe the case of a 17-year - old patient who was diagnosed with both cd and ankylosing spondylitis ( as ) , having undergone a long ileo - colonic anastomosis to treat hd at 12 months of age . to our knowledge , this is the first documented case of cd combined with as in a patient with hd .