bacterial , parasitic , viral infections and almost all of the immunosuppressive drugs used can produce diarrhea ; however , inflammatory bowel disease ( ibd ) is rare in the transplant recipient .
a 46-year - old man who developed end - stage renal disease ( esrd ) of unknown etiology underwent live related renal transplantation , with his sister as the donor in 1996 .
he was started on cyclosporine , azathioprine , and prednisolone , with cyclosporine being withdrawn 1 year after transplantation because of financial constraints .
subsequently , he was only on azathioprine ( 125 mg daily ) and prednisolone ( 15 mg on alternate days ) .
he had no episodes of graft dysfunction , post - transplant diabetes mellitus , malignancies , or opportunistic infections .
he developed diarrhea in 2005 , with four to five episodes of semi - formed stools a day .
he took symptomatic treatment for the same for two years . in 2007 , he noticed blood streaking of stools and lost about 5 kg of weight .
multiple stool cultures and examinations were negative for salmonella , shigella , campylobacter , clostridium difficile toxin , yersinia , enterotoxigenic e. coli , cryptosporidium , giardia , and strongyloides larvae .
colonoscopy revealed multiple 5 to 8 mm size superficial ulcers with edematous surrounding mucosa , with clean base and hyperemic margins up to 20 cm from the anal margin .
on histological examination , the rectal and sigmoid mucosa showed mucosal hyperplasia with crypt abscesses and evidence of acute and chronic inflammation [ figures 1 and 2 ] .
a diagnosis of ulcerative colitis was made and he was started on mesalamine 2 gm / day .
the frequency of stools decreased to 1 to 2 a day , with no blood or mucus .
active colitis with muco - depletion , cryptitis with crypt abcessess ( arrow ) ( h and e , 40 ) crypt distortion , crypt loss ( arrow ) , and interstitial inflammation with lymphomononuclear and eosinophilic infiltration ( chronic colitis ) ( h and e , 20 )
diarrhea is a common complication after transplantation , the incidence being as high as 12% .
an etiology for the diarrhea can be identified in 80% of the cases , with infections being the most common cause ( 41.5% ) followed by immunosuppressive medication ( 34% ) .
two - third of the diarrhea episodes develop in the late post - transplant period ( > 6 months after transplantation ) and 14% of the episodes are of chronic diarrhea .
the incidence of diarrhea is higher with mycophenolate mofetil ( mmf ) compared to azathioprine , tacrolimus compared to cyclosporine , and with sirolimus compared to azathioprine .
the dose dependence of diarrhea has been demonstrated with mmf and sirolimus , with higher doses associated with greater incidence of diarrhea .
combinations of immunosuppressive agents , while improving efficacy , may increase risk of diarrhea . for example , the incidence of diarrhea was increased but the rate of acute rejection was significantly less with the combination of mmf with tacrolimus , compared with the combination of mmf with cyclosporine . similarly , the combination of mmf with sirolimus was associated with three - fold increase in the incidence of diarrhea compared with its combination with cyclosporine . a stepwise increase in diarrhea
is noted from renal to cardiac to liver transplantation , and an overall higher incidence of diarrhea is seen in the white population .
ibd is an uncommon cause of diarrhea after transplantation and there are only few case reports of ibd developing de novo after kidney transplantation.[1315 ] passfall et al . in 1992
reported the first case of ulcerative colitis in a kidney transplant recipient while on monotherapy with cyclosporine .
this 60-year - old patient on cyclosporine alone after methylprednisolone being withdrawn 6 months post - transplantation presented with rectal bleeding 6 years after kidney transplantation .
the colonoscopy and histological features were consistent with ulcerative colitis and infectious causes were ruled out with extensive investigations .
the patient responded to re - introduction of methylprednisolone and cyclosporine was continued . in 1997 , riley et al . reported a case series of transplant recipients who developed ibd .
only two of the 14 cases reported in the series were kidney transplant recipients , the rest being liver transplant recipients .
the cause of esrd was obstructive uropathy in one and adpkd in the other patient .
both the patients were on cyclosporine and prednisolone and the dose of prednisolone at the onset of symptoms was less than 10 mg / day .
although one of the patients responded to treatment with azulfidine , the other continued to have intermittent flares despite increased doses of prednisolone .
the mean duration to the onset of symptoms after transplant in this series was 4 years and the presenting symptoms , in order of frequency , were bloody diarrhea ( seven ) , diarrhea ( five ) , abdominal cramping ( five ) , and bright red blood per rectum ( three ) .
reported a case of ulcerative colitis developing in a renal transplant recipient 4 years after transplantation .
the cause of esrd in this male child was anti - gbm disease and he received triple immunosuppression with cyclosporine , prednisolone , and azathioprine .
four years after transplantation , he developed bloody diarrhea which was presumed to be cmv enterocolitis as he was cmv seropositive after transplantation and colonic biopsy showed cmv inclusions .
he failed to respond to ganciclovir and required pancolectomy , which on histologic examination did not show any evidence of cmv but had features consistent with ulcerative colitis .
development of ibd while the patient is on immunosuppression is unexpected , because ibd is believed to be the result of inappropriate and ongoing activation of the mucosal immune system and immunosuppression is used in the treatment of ibd .
the most common situation in which association of transplantation with ibd is seen is with liver transplantation in primary sclerosing cholangitis(psc ) .
about 70% of patients with psc will develop ibd , which may be before transplantation or as de novo disease after liver transplantation . in the case series by riley et al . , the average time to ibd diagnosis after transplantation ( liver or kidney ) was four years and none of them presented in the first post - transplant year .
the authors hypothesized that this delay in presentation may be the result of lesser use of corticosteroids in the late post - transplant period .
a number of hypotheses have been put forward to explain the unexpected development of ibd while on immunosuppression .
the allograft may reconstitute a competent immune system in the recipient , and immunosuppressive therapy makes the patient susceptible to opportunistic infections which may trigger ibd manifestations .
both tacrolimus and cyclosporin a inhibit the peptidyl - prolyl isomerase enzyme activity and interfere with effective t cell intracellular signalling . in some predisposed individuals ,
tacrolimus or cyclosporin a may lead to reduction of the cd8 suppressor cells to a greater degree than other t cell populations , increasing the helper - to - suppressor ratio .
such a t cell imbalance has been reported to be an etiological factor in ibd.[142022 ] riley et al .
first is a case report of an hiv - positive patient with crohn 's disease whose ibd improved with decline in cd4 + cell count , thus decreasing the helper - to - suppressor ratio .
the second example mentions two patients with renal cell cancer who received exogenous interleukin-2 ( usually produced by activated t cells ) and developed a flare in their preexisting ibd .
these hypotheses explaining the development of ibd while on immunosuppression require further evaluation and validation .
our case is unique in that the patient was not receiving calcineurin inhibitors ( cnis ) for 8 years preceding the development of symptoms ; he was only on azathioprine and prednisolone and the above hypothesis do not apply in our case .
mechanisms other than the specific action of cnis on t cell function thus appear to play a role in pathogenesis of ibd while on immunosuppression .
 diarrhea is common after kidney transplantation and is usually related to immunosuppressive medication or is infective in etiology . 
 inflammatory bowel disease ( ibd ) is rare after kidney transplantation and is unexpected because the patient is already immunosuppressed . 
 specific immunomodulatory actions of calcineurin inhibitors have been hypothesized to play a role in the development of ibd in such patients . 
 we report a case of ibd developing de novo after kidney transplantation . 
 our case is unique in that the patient was not on calcineurin inhibitors for 8 years prior to the development of ibd . 
Introduction
Case Report
Discussion