crohn 's disease ( cd ) is a chronic inflammatory disorder of the gastro - intestinal tract [ 1 , 2 , 3 ] ; its exact aetiology and pathogenesis is not known .
current models of pathogenesis include interactions between genetic factors , environmental factors , and the intestinal flora which lead to dysregulation of the immune response and to inflammation of the wall of the gastro - intestinal tube [ 4 , 5 ] .
exacerbations are due to flares of inflammation of the wall of the gastro - intestinal tube .
inflammation in cd is transmural and segmental [ 1 , 4 , 6 ] ; thus it spares certain regions and leaves healthy mucosa between the affected , ulcerated sites .
transmural inflammation leads to the development of sinus tracts in the organ 's wall , which can lead to phlegmon , fistulas to neighbouring structures , and abscesses .
cd can affect any part of the gastro - intestinal tract from the mouth to the anus , but it most often affects the terminal ileum and the colon [ 3 , 4 ] .
over 70% of patients have small bowel involvement , usually of the terminal ileum . about 40% of patients have ileo - colic disease , and 30% present with small intestinal disease .
cd of the upper gastro - intestinal tract ( oesophagus , stomach , and duodenum ) is much less frequent and most often associated with involvement of more distal parts of the gastro - intestinal tract [ 1 , 7 , 8 ] .
further , upper gastro - intestinal disease may be associated with progression and recurrence of intestinal disease [ 6 , 9 ] .
the literature shows variable data regarding the prevalence of upper gastro - intestinal involvement ranging from 0.2 to 16% [ 1 , 3 , 4 , 5 , 6 , 7 , 8 , 9 ] .
however , isolated oesophageal cd is a very rare condition [ 1 , 2 , 3 , 7 , 10 , 11 ] . the clinical presentation and endoscopic and histologic findings of oesophageal cd are mostly non - specific and share features of more common diseases of the oesophagus .
therefore , accurate diagnosis of oesophageal cd can be very challenging [ 9 , 10 , 11 ] and is often made late in its course [ 2 , 10 ] . in the following
we report the case of a relapsing para - oesophageal abscess posing a great diagnostic challenge .
a 42-year - old male patient with a para - oesophageal abscess and a fistula into the distal oesophagus was referred to our gastroenterology department in september 2012 for further evaluation and treatment .
the past medical history consisted of chronic back pain in the context of a lumbar disc herniation , for which he underwent spinal fusion surgery .
[ non - steroidal anti - inflammatory drug ( nsaid ) ] and esomeprazole 40 mg q.d .
our patient complained of progressive epigastric pain that did not improve after the nsaid had been withdrawn and esomeprazole was increased to 40 mg b.i.d . on admission
he was febrile ( 38.3c ) , palpation of the epigastric region was tender , and laboratory studies showed inflammatory changes with a leucocyte count of 15.6  10/l ( normal value 410  10/l ) , a left shift of neutrophils of 28% ( normal value < 16 ) , and an elevated c - reactive protein ( crp ) level of 282 mg / l ( normal value < 5 ) .
thoraco - abdominal computed tomography ( ct ) revealed a para - oesophageal abscess with a maximal extension of 6 cm adjacent to the oesophago - gastric junction and a fistula into the distal part of the oesophagus ( fig .
1 ) . upper endoscopy showed the fistula 's porus at 39 cm from the tooth row ; otherwise the mucosa of the oesophagus , stomach , and duodenum was normal .
we performed an endoscopic ultrasound ( eus ) that revealed an asymmetrical thickening of the oesophageal wall adjacent to the abscess , which caused a narrowing of the lumen .
histologic specimens taken from the oesophagus revealed chronic inflammation with a preponderance of granulocyte infiltration .
we continued treatment with the ppi and inserted a naso - duodenal tube for enteral nutrition .
further , we started an intravenous antibiotic therapy with amoxicillin 2,000 mg and clavulanic acid 200 mg t.i.d .
endoscopy combined with eus confirmed the complete resolution of the fistula and the abscess , whereas the thickening of the oesophageal wall and the enlarged lymph nodes persisted .
because of a possible malignancy , a follow - up endoscopy was performed 2 and 5 months after discharge . only a little
pseudo - diverticula remained at the site of the former fistula , the thickening of the oesophageal wall had resolved completely , no other mass could be detected , and the mucosa appeared normal .
however , more distally , a partial stenosis remained , impeding the passage of the eus endoscope .
as the cause of the abscess remained unclear , we supposed the previous treatment with the nsaid as a possible trigger .
oesophageal contrast examination revealed stenosis at the oesophago - gastric junction with a lack of relaxation of the lower oesophageal sphincter documented by high - resolution manometry .
two balloon dilations ( 30-mm savary balloon ) achieved good control of the complaints in the following months . after a symptom - free period of 18 months , the patient was referred to our emergency department due to a rapidly progressive odynophagia impeding oral intake of food or fluids . on admission
the patient was afebrile ( 36.8c ) and in a poor general state ; blood pressure ( 117/75 mm hg ) and heart rate ( 80 bpm ) were within the normal range .
bowel sounds were clearly audible , and palpation of the epigastric region provoked tenderness , but there were no signs of peritonism . otherwise , the clinical examination showed normal findings .
laboratory studies revealed inflammatory changes with a leucocyte count of 13.2  10/l and an elevated crp level of 139 mg / l .
ct scanning of the thorax and the upper abdomen detected a para - oesophageal air - containing fluid collection of 3.5 cm with an enhancing wall at the same location as the previous abscess had been .
the histologic specimen of the oesophagus revealed acute - on - chronic inflammation with ulceration and granulation .
again , there was no evidence of an eosinophilic oesophagitis , a tumorous growth , or a fungal infection . in the stomach ,
minimal non - active unspecific inflammation was detected , and the histology of the duodenum had a normal aspect .
culture showed a mixed growth of aerobe and anaerobe bacteria as well as some yeast .
a serologic examination for human immunodeficiency virus ( hiv ) was negative ( hiv-1/2 antigen - antibody chemiluminescent microparticle immunoassay ) .
studies for cytomegalovirus ( cmv ) revealed undetectable cmv igm , and cmv igg was 138 ae / ml ( normal value < 6 ) . also for varicella zoster virus ( vzv ) , igm was negative and vzv igg was 740
serologic studies for herpes simplex virus ( hsv ) types 1 and 2 showed a raised hsv1/2 igg titre of 41,000 ( normal value < 230 ) and an indeterminate testing for hsv1/2 igm .
thus the results regarding hsv types 1 and 2 , vzv , and cmv were consistent with a past infection .
anti - saccharomyces cerevisiae antibody igg and iga were positive ( igg 10 u / ml , iga 11 u / ml ; normal value < 7 ) .
titre of anti - neutrophil cytoplasmic antibody was normal ( normal value < 1 : 20 ) , whereas titre of anti - nuclear antibody was slightly raised ( > 1 : 80 ; normal value < 1 : 80 ) .
helicobacter pylori serology was within normal range ( igg < 10 e / ml ; normal value < 10 ) .
the histologic specimens of the terminal ileum , colon , and rectum did not show evidence of a chronic inflammatory disease .
mri of the small intestine also showed normal findings . based on the current endoscopic , histologic , and
also serologic findings and preclusion of other diseases , we made the diagnosis of cd with isolated involvement of the oesophagus complicated by a recurrent para - oesophageal abscess .
we started intravenous antibiotic treatment with amoxicillin 2,000 mg and clavulanic acid 200 mg t.i.d . for 20 days and then changed to an oral regimen of amoxicillin 500 mg and clavulanic acid 125 mg t.i.d .
the symptoms resolved rapidly , and the leucocyte count and crp level returned to normal .
upper endoscopy with eus performed after 2 weeks of treatment showed only a small residual of the abscess .
after 3 days . currently , the patient is treated with azathioprine alone and is still in remission .
there are only limited data available regarding the prevalence of oesophageal cd , and the prevalence of upper gastro - intestinal involvement is estimated to be 0.216% in patients with co - existing ileo - colic cd [ 1 , 3 , 4 , 5 , 6 , 7 , 8 , 9 ] .
not all patients with cd undergo upper endoscopy ; therefore its prevalence might be underestimated [ 8 , 9 , 11 ] . on the other hand ,
different study populations are analysed , and also different diagnostic criteria are used to define cd involvement of the upper gastro - intestinal tract and oesophagus .
furthermore , the prevalence of upper gastro - intestinal involvement has increased since the 1990s compared to older reports [ 1 , 5 , 12 ] .
this is probably due to wider use of endoscopy for clinical staging and research as well as better diagnostic tools [ 7 , 12 ] .
the clinical presentation of oesophageal cd varies , ranging from asymptomatic [ 1 , 7 , 12 ] to serious illness [ 2 , 3 , 7 , 8 , 9 , 10 , 13 ] .
complications include strictures and stenosis [ 1 , 7 , 10 , 11 , 14 ] , abscesses , and fistulas to neighbouring organs [ 2 , 11 ] such as the respiratory tract [ 1 , 13 ] .
as reported by our patient , symptoms are often unspecific in oesophageal cd , resembling those of other oesophageal diseases .
most often , patients complain of dysphagia , odynophagia , retrosternal pain , or discomfort [ 1 , 2 , 3 , 4 , 7 , 8 , 10 , 11 , 13 ] .
since most cases of oesophageal cd occur in patients with known cd or concurrent intestinal cd , diagnostic procedures may lead towards the correct diagnosis .
the diagnostic challenge in our case was the fact that there were no findings to support the diagnosis of cd at the time of first presentation .
typical symptoms of intestinal cd ( e.g. , crampy lower abdominal pain or change of bowel habits such as diarrhoea or bloody stool ) . at first presentation ,
upper endoscopy revealed only the fistula 's porus ; apart from that there was no evidence of a diffuse inflammatory process .
almost 3 years later , disseminated oesophageal ulcerations became evident for the first time and raised a high suspicion of cd .
the endoscopic and macroscopic findings of oesophageal cd described in the literature range from mild mucosal hyperaemia and superficial aphthous ulcers [ 3 , 8 ] in early disease stages to deep ulcerations and erosions , fistulas , and cobblestone appearance in more advanced disease stages [ 1 , 3 , 5 , 7 , 8 , 9 , 10 , 11 , 14 ] .
differential diagnosis of oesophageal cd is broad and includes other causes of oesophageal disease like gastro - oesophageal reflux disease and eosinophilic oesophagitis , drug - induced oesophagitis , viral and fungal infections , tuberculosis , epidermolysis bullosa acquisita , connective tissue disease , and vasculitis as well as malignancy [ 1 , 4 , 8 , 11 ] . in our case
non - caseating granulomas are considered to be specific to cd ; however , they are found in less than 40% of biopsies taken from the oesophagus [ 3 , 4 , 5 , 7 , 8 , 11 ] .
the histologic findings did therefore not allow endorsing or excluding the diagnosis of cd ; however , chronic and acute - on - chronic inflammation is , although not specific , associated with oesophageal cd [ 1 , 2 , 3 , 7 , 8 , 9 , 10 ] . on the other hand , histology allowed us to exclude other possible causes . malignancy and
but since the thickening of the oesophageal wall had resolved , no other mass became evident , and repeated histologic specimens never provided evidence of malignant cells or eosinophilic infiltration , malignancy as well as eosinophilic oesophagitis seemed very unlikely to be the underlying cause .
our immunologic examinations for hsv , cmv , vzv , and hiv did not show active infection , and histologically there was no evidence of fungal infection or viral cytopathic effects .
signs of a multi - system disease such as connective tissue disease or vasculitis were not evident .
ileo - colonoscopy and mri - enterography did not reveal chronic intestinal inflammation ; only some cicatrized sites in the terminal ileum were found . whether they represented the residual of a past , somehow asymptomatic or subclinical
inflammation remains unclear . in view of the clinical history of relapsing abscess formation and fistulization , the macroscopic aspect of diffuse ulcerative lesions , histologically chronic and acute inflammation , the positive anti - saccharomyces cerevisiae antibody titre as well as the lack of other aetiologies , we established the diagnosis of isolated oesophageal cd .
regarding the treatment of oesophageal cd there are no randomized controlled trials ; evidence is based on case series [ 1 , 4 , 7 , 12 ] .
the european crohn 's and colitis organization ( ecco ) proposes ppi for the treatment of oesophageal and gastroduodenal cd .
depending on the severity of the disease , ppi can be combined with systemic corticoids , thiopurines , or methotrexate .
most authors propose dilation with or without steroid injections for strictures [ 1 , 8 , 9 , 11 , 12 ] , and surgery remains an option for refractory strictures as well as fistulas and abscesses which can not be managed otherwise .
some concerns exist that ppi as sole treatment might not be sufficient , since the inflammatory process is not inhibited [ 8 , 15 ] .
our patient had been under ppi treatment even before he developed the abscess and the stricture .
diagnosis of isolated oesophageal cd can be challenging [ 3 , 8 , 9 , 11 ] , since clinical findings often are non - specific .
the diagnosis has to be made by integration of symptoms as well as endoscopic , histologic , and serologic findings [ 3 , 8 , 9 , 11 ] .
other , more frequent diseases ( e.g. , malignancy , eosinophilic oesophagitis , and viral or fungal infections ) must be ruled out .
 oesophageal involvement in crohn 's disease ( cd ) is uncommon and most often accompanied by involvement of more distal parts . 
 its presentation is mostly non - specific , and therefore a diagnosis , especially in isolated oesophageal disease , is difficult . 
 we present the case of a 42-year - old male patient who was referred to our gastroenterology department because of a para - oesophageal abscess . under antibiotic treatment 
 the abscess healed , but despite great diagnostic efforts , its aetiology remained unclear . 
 three years later the patient was hospitalized again because of an abscess at the same site . 
 endoscopy showed disseminated ulcerations of the lower oesophagus , raising suspicion of cd . after excluding other possible causes 
 , we made the diagnosis of isolated cd of the oesophagus . 
 we review the available literature on this topic and discuss the clinical presentation , symptoms , endoscopic findings , and histology as well as treatment of oesophageal cd . 