a rising trend in the incidence and prevalence of inflammatory bowel disease ( ibd ) in asia has been recognized for the past two decades .
the thiopurine drugs azathioprine ( aza ) and mercaptopurine are widely used for the treatment of ibd and have proven to be effective in both inducing and maintaining remission of crohn 's disease and ulcerative colitis ; however adverse effects can occur in 928% of patients , and these adverse effects often necessitate a dose reduction or discontinuation .
nevertheless , some reports suggested that neutropenia during aza therapy reduced the relapse rates in ibd patients [ 1 , 2 ] , and that the eradication of sensitized leukocytes , which was done by leukapheresis or bone marrow transplantation , improved ibd in some cases [ 3 , 4 ] .
there have also been some cases of ulcerative colitis with prolonged remission following aza - induced pancytopenia [ 5 , 6 ] .
a 22-year - old man with a known history of crohn 's colitis who had undergone fistulectomy for complex perianal fistula 2 years previously was admitted with a complaint of severe weight loss ( 25 kg during 2 years ) , diarrhea , abdominal pain and recurrent perianal tenderness .
physical exam revealed fistular openings and subcutaneous abscess pockets with severe tenderness on the anus and buttock .
he was not able to maintain a sitting or supine position , so his social activity was limited .
contrast - enhanced computed tomography scan of the abdomen showed multifocal inflammatory wall thickening and thick - walled abscess pockets with the beaded appearance of subcutaneous small abscesses in the precoccygeal and perianal area ( fig .
abscess drainage and a seton operation were performed , then aza was administered at a starting dose of 25 mg ; this was increased up to 50 mg after 2 weeks .
he then revisited the hospital and presented with high fever ( 39.2c ) and myalgia . on general peripheral blood test , leukocytes were 180/l ( segmented cells 6% ) , hemoglobin was 6.6 g / dl and platelets were 48,000/l .
after 2 weeks of administering human recombinant granulocyte colony - stimulating factor and broad - spectrum antibiotic therapy , his fever subsided and the cell count fully recovered .
escherichia coli was found on blood culture , but it was sensitive to the antibiotics .
after recovering from cytopenia , the frequency of bowel movements decreased and the perianal pain and oozing improved gradually .
follow - up colonoscopy was performed 3 months later and demonstrated diffuse fibrotic scar instead of multiple ulcerations ( fig .
he gained 10 kg within 6 months and is now on regular follow - up without clinical recurrence ( cdai score = 114 ) .
therefore , a conventional immunosuppressive dose of less than 2.5 mg / kg / day causes predictable mild leukopenia .
rarely however , sudden , severe and unexpected myelosuppression , which is possibly idiosyncratic , has also been reported when low to moderate doses ( < 2 mg / kg / day ) of the drug were used . in these cases ,
the cytopenic patients are vulnerable to the development of sepsis that necessitates hospital admission for intensive care .
however , the preferential suppression of neutrophils develops when leukopenia occurs , which suggests that aza 's antiinflammatory effects are mediated through its effects on neutrophils as well .
in fact , clinical relapse of ibd is characterized by increased neutrophil migration into the intestine .
. moreover , some reports have described cases of ulcerative colitis with prolonged remission following pancytopenia .
burke et al . reported prolonged remission in excess of 4 years following induced pancytopenia , where 3 of the 4 patients who developed severe neutropenia remained in remission for up to 21 months following that episode .
first , given that altered host immunity plays an important role in ibd activity , it is possible that this patient 's host immunity was reset following the pancytopenia caused by aza . according to one report that analyzed the course of patients with crohn 's disease and ulcerative colitis and who underwent allogeneic stem cell transplantation for myeloid leukemia and myelodysplastic syndrome , 10 of 11 patients showed no ibd activity after stem cell transplantation , and the colonoscopy after complete discontinuation of prophylactic posttransplant immunosuppression revealed no pathologic findings .
second , the possible benefit of granulocyte macrophage colony - stimulating factor ( gm - csf ) can be hypothesized .
dieckgraefe and korzenik investigated the safety and possible benefit of gm - csf for the treatment of 15 patients with moderate to severe crohn 's disease .
third , the original bowel flora is temporarily altered after total gut decontamination and long - term antibacterial treatment .
therefore , the most likely theory seems to be the modification of a genetically determined immune abnormality that is responsible for the chronic intestinal inflammation by the reset of the immune system or modification of an altered microbial environment .
however , it is unclear whether this mechanism can affect the long - term clinical course .
some studies have reported that tpmt genotype or activity does not predict the development of aza - induced myelotoxicity . on the other hand ,
some reports have suggested a substantial correlation between low enzyme activity and the development of myelotoxicity [ 13 , 14 ] .
reported that assessment of the tpmt genotype or activity can reduce the risk of myelotoxicity in approximately one - third of patients . in our case ,
the tpmt was the wild type and this result raised doubts whether tpmt can be a reasonable screening test to identify patients with a high risk of severe myelotoxicity due to an inherited deficiency of tpmt activity . in conclusion , we report here a patient who had crohn 's colitis and complicated perianal fistulas that required immunosuppression , and who achieved endoscopically determined remission that showed accelerated mucosal healing as well as clinical remission after aza - induced pancytopenia .
 the immunosuppressant azathioprine ( aza ) is widely used in the treatment of inflammatory bowel disease ( ibd ) for both inducing and maintaining remission . 
 however , the adverse effects of aza can often necessitate a dose reduction or discontinuation . 
 bone marrow suppression is one of the most serious complications with aza treatment . on the other hand , 
 some reports have suggested that neutropenia during aza therapy reduced the relapse rates of ibd patients , and there have been some cases where eradication of the sensitized leukocytes by leukapheresis or bone marrow transplantation improved the ibd , which may explain the relevant role of neutropenia in controlling disease activity . 
 this report describes the case of a 22-year - old male patient who had crohn 's colitis and complicated perianal fistulas that required immunosuppression ; he achieved endoscopically determined remission and showed accelerated mucosal healing as well as clinical remission following the aza - induced pancytopenia . 
Introduction
Case Report
Discussion