What is the differential diagnosis of diarrhea following solid organ transplantation?
Diarrhea is a frequent complication after transplantation, with 3-year posttransplant cumulative incidence reported to be around 22%. It has been associated with worse clinical outcomes, including acute kidney injury (AKI), supratherapeutic tacrolimus and mycophenolate levels, and decreased graft and patient survival.
The most common causes of diarrhea in patients after transplantation include infections, immunosuppressive medications, and antibiotics.
Noninfectious diarrhea in patients after transplantation
is commonly due to immunosuppressive drugs, with the highest incidence associated with mycophenolic acid.
Notably, patients with combined kidney-pancreas transplants are at a greater risk for rejectionand thushave higher exposure to immunosuppression compared to those with other solid organ transplants. Infectious diarrhea following kidney transplantation is frequently attributed to Clostridium difficile, CMV, and norovirus
What should be included in the diagnostic evaluation of diarrhea in patients after transplantation?
Current guidelines for evaluation of diarrhea in solid-organ transplant recipients from the Infectious Disease Community of Practice of the American Society of Transplantation start with stopping any nonimmunosuppressive medications that may cause diarrhea—such as proton pump inhibitors, H2
agonists,
and oral hypoglycemics—and first-line microbiological testing including Clostridium difficile polymerase chain reaction (PCR), CMV PCR, and multiplex PCR if available
What is the most likely explanation for this patient’s diarrhea?
Given the positive stool PCR, the most likely diagnosis is sapovirus infection resulting in acute worsening of chronic diarrhea. Several recent case reports have described sapovirus
infections leading to chronic, severe diarrhea in patients after kidney transplant.
How should this patient be managed?
Reducing mycophenolate dosage in response to posttransplant diarrhea is a common practice and has been shown to have some efficacy in patients with persistent diarrhea regardless of cause. However, caution should be used when opting for this treatment strategy, as reductions in mycophenolate dose have also been shown to be associated with rejection and decreased allograft survival.10 Other possible treatment options include switching mycophenolic acid to an enteric-coated mycophenolate or azathioprine, both of which have been associated with a lower risk of developing posttransplant diarrhea.
This patient was managed with intravenous fluids
and reduction of his mycophenolate dosage from 720 mg twice a day to 360 mg twice a day. By hospital day 3, his serum creatinine had returned to baseline with interval improvement of acute diarrhea. At 3 weeks follow-up, the patient showed marked clinical improvement, with 2 to 3 kg of weight gain and complete resolution of his acute-on-chronic diarrhea.
Non-infectious causes: · Immunosuppressive medications such as mycophenolate, tacrolimus, cyclosporine, sirolimus, proton pump inhibitors, protease inhibitors
Post-transplant lymphoproliferative disease
inflammatory bowel disease
Graft vs host disease
malabsorption
colon cancer
2. Diagnostic evaluation of post-transplant diarrhoea
identify cause of post-transplant diarrhoea
stop non-immunosuppressive medications that can cause diarrhoea like proton pump inhibitors, H2 agonists, oral hypoglycemic drugs
first line microbiological testing includes Stool tests for ova, cysts, culture to isolate bacteria; Clostridium difficile toxins A & B – EIA; PCR for C. Defficile, CMV, multiplex multi-viral PCR.
If first line microbiological tests are negative à second round of microbiological testing include Stool PCR for viral pathogens, ova, and parasite evaluation, giardia and cryptosporidium enzyme immunoassay; breath test for bacterial overgrowth.
Likely explanation for post-transplant diarrhoea In the index case, the patient’s tacrolimus level was found to be within acceptable limits. First line microbiological testing was negative. Stool ova and parasite along with stool culture were also negative. However, fecal multiplex PCR was positive for sapo-virus, which could have been the reason for acute worsening of chronic diarrhoea in this patient. Management of the patient Sapovirus infection – a non-enveloped single stranded positive sense RNA virus. Management includes Ø Hydration Oral (intravenous, if poor oral intake or acutely ill) Ø MPA dose reduction – allows immune system to clear infection Ø Tacrolimus C0 levels monitoring – enterocyte damage can lead to increased serum tacrolimus levels Ø Nitazoxanide – activates natural antiviral defence and inhibits cellular pathways that aid in viral replication Ø If reduction in MPA dosage doesn’t help to clear viral infection but required further reduction, it cannot be done since this can damage the graft. In this case, consider switching to enteric coated mycophenolate, or azathioprine. Ø Anti motility agents – loperamide, after treatment of pathogen. Ø Follow up for patient’s appetite, weight gain, volume status, renal functions on frequent basis.
Non infectious causes include IS medications such as mycophenolate, tacrolimus, cyclosporine, sirolimus, proton pump inhibitors, protease inhibitors
Graft vs host disease
post transplant lymphoproliferative disease
inflammatory bowel disease
colon cancer
malabsorption
Diagnostic evaluation of post transplant diarrhoea
identify cause of post transplant diarrhoea
stop non-immunosuppressive medications that can cause diarrhoea like proton pump inhibitors, H2 agonists, oral hypoglycemics
first line microbiological testing includes clostridium difficile PCR, CMV PCR, multiplex PCR
If first line microbiological testing comes back negative, then second round of microbiological testing will include stool PCR for viral pathogen, ova, and parasite evaluation, giardia and cryptosporidium enzyme immunoassay; breath test for bacterial overgrowth
Likely explanation for post transplant diarrhoea
In the case discussed in the given article, the patient’s tacrolimus level was found to be within acceptable limits. First line microbiological testing was negative. Stool ova and parasite along with stool culture were also negative. However, on fecal multiplex PCR investigation, the patient was found to be positive for sapovirus. This should have been the reason for acute worsening of chronic diarrhoea that this patient had.
Management
This patient has sapovirus infection. Sapovirus is a non-enveloped single stranded positive sense RNA virus.
IV fluids
reduction of MPA dosage – allows immune system to clear infection
anti motility agents – loperamide
monitor tacrolimus levels since enterocyte damage can lead to increased serum tacrolimus levels
nitazoxanide – activates natural antiviral defense and inhibits cellular pathways that aid in viral replication
If reduction in MPA dosage doesn’t help to clear viral infection but required further reduction, it cannot be done since this can damage the graft. In this case, consider switching to enteric coated mycophenolate, or azathioprine.
What is the differential diagnosis of diarrhoea following solid organ transplantation?
After transplantation, diarrhea is a common complication, with a 3-year cumulative incidence of diarrhea being reported to be approximately 22%.
Patients who have received a solid organ transplant are susceptible to infections, immunosuppressive drugs, and antibiotic-induced diarrhea.
Immunosuppressive medications frequently cause non-infectious diarrhea in transplant recipients, with mycophenolic acid having the greatest prevalence.
The common causes of infectious diarrhea after kidney donation include Clostridium difficile, CMV, and norovirus.
What should be included in the diagnostic evaluation of posttransplant diarrhoea?
Analyzing the root of diarrhea in a kidney transplant patient is crucial.
The first step in evaluating diarrhea in solid-organ transplant recipients according to current guidelines is to cease taking any non-immunosuppressive drugs that can make them sick.
If available, multiplex PCR, CMV PCR, and Clostridium difficile PCR are among the first-line microbiological tests.
Stool PCR for the assessment of viral pathogens, ova, and parasites, giardia and cryptosporidium enzyme immunoassay, and breath test for bacterial overgrowth should all be included in second-tier microbiological testing.
Differential diagnosis for post renal Transplant Diarrhoea:
Infectious
•Bacterial (Clostridium difficile, Campylobacter spp., Salmonella spp., Bacterial overgrowth, Aeromonas spp., Escherichia coli)
•Viruses (CMV, Norovirus, Sapovirus, Rotavirus, Adenovirus, Enterovirus)
• Parasitic (Giardia, Cryptosporidium, Isosdpora, Cyclospora, Microsporidium, Entamoeba) Noninfectious
•Immunosuppressive medications (Mycophenolate, Tacrolimus, Cyclosporine, Sirolimus)
•Nonimmunosuppressive medications as; Antibacterial, Antiarrhythmic, Antidiabetics, Laxatives, Proton pump inhibitors, Protease inhibitors)
•Other: GVHD, PTLD, IBD, Colon cancer, Malabsorption. The diagnostic evaluation of post-transplant diarrhoea should include:
Stopping any non-immunosuppressive medications that may cause diarrhea as proton pump inhibitors, H2 agonists and oral hypoglycemics.
First-line microbiological testing including Clostridium difficile polymerase chain reaction (PCR), CMV PCR, and multiplex PCR if available.
Stool PCR for viral pathogen, ova, and parasite evaluation; giardia and cryptosporidium enzyme immunoassay; and breath test for bacterial overgrowth.
Colonoscopy and biopsy may be needed in some situations. The most likely explanation for this patient’s diarrhoea
Is confirmed by positive stool PCR for Sapovirus infection resulting in acute worsening of chronic diarrhea. Management should be:
Symptom relief with intravenous fluids for volume repletion and antimotility agents such as loperamide.
Reduction of immunosuppression especially the antimetabolite mycophenolate dosage.
Tacrolimus levels should be closely monitored.
Nitazoxanide can be tried as it is an antimicrobial agent with an antiviral effect by activating natural antiviral defenses and inhibiting cellular replication pathways.
Follow up for the patient’s appetite, weight gain, volume status, renal functions on frequent basis.
What is the differential diagnosis of diarrhoea following solid organ transplantation?The differential diagnosis of diarrhea following solid organ transplantation includes various infectious and noninfectious causes:
Infectious causes:
Bacteria:Clostridium difficile
Campylobacter spp.
Salmonella spp.
Bacterial overgrowth
Aeromonas spp.
Escherichia coli
Viruses:Cytomegalovirus (CMV)
Norovirus
Sapovirus
Rotavirus
Adenovirus
Enterovirus
Parasitic:Giardia
Cryptosporidium
Isospora, Cyclospora
Microsporidium
Entamoeba
Noninfectious causes:
Immunosuppressive medications:Mycophenolate
Tacrolimus
Cyclosporine
Sirolimus
Nonimmunosuppressive medications:Antibacterial
Antiarrhythmic
Antidiabetic
Laxatives
Proton pump inhibitors
Protease inhibitors
Other causes:Graft-versus-host disease (GVHD)
Posttransplant lymphoproliferative disease (PTLD)
Inflammatory bowel disease (IBD)
Colon cancer
Malabsorption
What should be included in the diagnostic evaluation of posttransplant diarrhoea?The diagnostic evaluation of posttransplant diarrhea in solid-organ transplant recipients should include the following steps:
Stop any nonimmunosuppressive medications that may cause diarrhea, such as proton pump inhibitors, H2 agonists, and oral hypoglycemics.
If the first-line tests return negative results, proceed with second-tier microbiological testing:
Stool PCR for viral pathogens
Ova and parasite evaluation
Giardia and cryptosporidium enzyme immunoassay
Breath test for bacterial overgrowth
If further testing also gives negative results, consider additional diagnostic evaluations based on the patient’s clinical presentation and risk factors.
What is the most likely explanation for this patient’s diarrhoea?In the given case, the most likely explanation for the patient’s diarrhea is sapovirus infection, which resulted in acute worsening of chronic diarrhea. This conclusion is based on the positive stool PCR for sapovirus. How should this patient be managed?
No specific therapies have been proven effective in treating sapovirus infections, but symptom relief can be achieved with intravenous fluids, antimotility agents, and reduction of immunosuppression.
Monitoring tacrolimus levels is important as enterocyte damage can lead to increased serum levels.
Reducing mycophenolate dosage can help with persistent diarrhea but can be associated with rejection and decreased allograft survival.
The patient was treated with intravenous fluids and reduction of mycophenolate dosage, resulting in improvement and resolution of diarrhea.
What is the differential diagnosis of diarrhoea following solid organ transplantation?
Diarrhea is a frequent complication after transplantation, with 3-year post-transplant cumulative incidence reported to be around 22%.
Causes of diarrhea in a patient with a solid organ transplant include infections, immunosuppressive medications, and antibiotics.
Noninfectious diarrhea in patients after transplantation is commonly due to immunosuppressive drugs, with the highest incidence associated with mycophenolic acid.
Infectious diarrhea following kidney transplantation is frequently attributed to Clostridium difficile, CMV, and norovirus.
What should be included in the diagnostic evaluation of posttransplant diarrhoea?
It is critical to evaluate the cause of diarrhea in a kidney transplant recipient.
Current guidelines for evaluation of diarrhea in solid-organ transplant recipients start with stopping any nonimmunosuppressive medications that may cause diarrhea.
First-line microbiological testing includes Clostridium difficile PCR, CMV PCR, and multiplex PCR if available.
Second-tier microbiological testing should include stool PCR for viral pathogen, ova, and parasite evaluation; giardia and cryptosporidium enzyme immunoassay; and breath test for bacterial overgrowth.
Figure 1 in case report outlines a stepwise diagnostic algorithm with additional considerations if this further testing also gives negative results.
What is the most likely explanation for this patient’s diarrhoea? Since the patients clinical history and investigations are not supportive of any evidence of infection with a bakground of prolonged hiustory, it is likely non-infectious diarrhoea due to MMF
How should this patient be managed?
Treatment options for sapovirus infection include intravenous fluids, antimotility agents such as loperamide, reduction of immunosuppression, and monitoring of tacrolimus levels.
Reducing mycophenolate dosage in response to post-transplant diarrhea is a common practice and has been shown to have some efficacy in patients with persistent diarrhea regardless of cause.
Other possible treatment options include switching mycophenolic acid to an enteric-coated mycophenolate or azathioprine, both of which have been associated with a lower risk of developing post-transplant diarrhea.
What should include in diagnosis evaluation of post-transplant diarrhoea?
Discontinuation of any non-immunosuppression drug that can cause diarrhoea as PPI, H2 agonist & oral hypoglycaemic drugs.
Initial microbiological test: C. difficile PCR, CMV PCR, bacterial culture or PCR for bacteria & multiplex PCR if available.
Further microbiological test: Stool PCR for virus, ova & parasitize evaluation e.g. giardiasis & cryptosporidium enzyme immunoassay & breath test for bacterial overgrowth (if first line test result were negative).
EGD & colonoscopy with biopsy if there is suspicion of PTLD, CMV D+/R-, bloody diarrhoea or family history of IBD.
What is the most likely explanation of this patient diarrhoea:
Tac level is within target level.
Initial microbiological test result was negative.
Stool ova, parasite & stool culture were negative.
Faecal multiplex PCR was positive for saprovirus
So the most likely diagnosis is saprovirus infection which can cause acute worsening of chronic diarrhea.
Saprovirus belongs to norvovirus family & its prevalence among post-transplant patients is unknown.
How should this patient have managed?
No effective treatment of saprovirus infection
IV fluid, anti-motilityif non-infectious causes ruled out & reduction in IS can relief symptoms & clearance of virus.
Tac level should be monitored closely (enterocytic damage cause increase Tac level).
Nitazoxanide efficacy evidence is limited.
Reduce mycophenolate dose is common with some benefit regardless cause of diarrhoea( but risk of rejection increased).
Diarrhoea in a Patient with Combined Kidney-Pancreas Transplant DDX
Infection;
Bacterial- C.difficile, campylobacter, salmonella, aeromonous,E.choli and bacterial overgrowth.
Viral – CMV, adenovirus, sapovirus, rotavirus, norovirus, enetrovirus etc.
Parasitic -giardia,isospora,cyclospora,cryptosporidium,entamoeba,microsporidia etc.
Non infectious;
Medication; MMF, CNI, MTORi, antibacterials, antiarrythmics, anti diabetics, laxatives, PPIs, PI etc
Others ;GVHD,PTLD,IBD, Colon Ca, Malabsorption etc..
Inclusion in diagnostic tests;
Stop any non immunosuppressive meds that might contribute to diarrhea.
Antimicrobiological testing for C.difficile PCR,CMV PCR and multiplex PCR, if negative, stool PCR for viral pathogen, giardia, cryptosporidium enzyme immunoassay and breath tests for bacterial overgrowth.
■ What should be included in the diagnostic evaluation of posttransplant diarrhoea?
☆ Microbiological testing including Clostridium difficile PCR , CMV PCR, and multiplex PCR if available
☆ Stool PCR for viral pathogen, ova, and parasite evaluation; giardia and cryptosporidium enzyme immunoassay
☆ Breath test for bacterial overgrowth.
☆ Biopsy
☆ CMV IgM and or elevation in IgG
☆ Conventional culture
☆ Shell Vial assay
☆ CMV pp65 Ag
■ What is the most likely explanation for this patient’s diarrhoea?
Infections diarrhea with Sapobavirus that persist by immunosuppression drugs especially MMF
■ How should this patient be managed?
☆ Intravenous fluids
☆ Antimotility agents such as loperamide,
☆ Reduction of immunosuppression
☆ Monitore tacrolimus levels closely
☆ Antimicrobial agent as Nitazoxanide which activating natural antiviral defenses and inhibiting cellular pathways leading to viral replication
What is the differential diagnosis of diarrhea following solid organ transplantation? Infectious 1-Bacteria: Clostridium difficile, Campylobacter spp, Salmonella spp, Bacterial overgrowth, Aeromonas spp, Escherichia coli 2-Viruses : CMV , Norovirus, Sapovirus , Rotavirus, Adenovirus , Enterovirus 3-Parasitic : Giardia, Cryptosporidium , Isospora, Cyclospora , Microsporidium ,Entamoeba Noninfectious 1- Immunosuppressive medications Mycophenolate Tacrolimus, Cyclosporine, Sirolimus 2- Nonimmunosuppressive medications: Antibacterial, Antiarrhythmic, Antidiabetic, Laxatives, Proton pump inhibitors, Protease inhibitors 3- Other: GVHD , PTLD , IBD , Colon cancer, Malabsorption 2- What should be included in the diagnostic evaluation of posttransplant diarrhea?
first-line microbiological testing including Clostridium difficile polymerase chain reaction (PCR), CMV PCR, and multiplex PCR if available .If these tests return negative results, second-tier microbiological testing should include stool PCR for viral pathogen, ova, and parasite evaluation; giardia and cryptosporidium enzyme immunoassay; and breath test for bacterial overgrowth. 3- What is the most likely explanation for this patient’s diarrhea?
Given the positive stool PCR, the most likely diagnosis is sapovirus infection resulting in acute worsening of chronic diarrhea. 4-How should this patient be managed?
1) Good hydration with IV fluid.
2) Antimotility agents such as loperamide.
3) Reduction of immunosuppression to promote the immune system to clear the viral infection.
4) Nitazoxanide which is an antimicrobial agent that exerts its effect on viruses.
5) Close monitoring of tacrolimus.
2. What should be included in the diagnostic evaluation of posttransplant diarrhoea?
1- Clinical assessment to role out infection and new drugs
2- Start with stopping any non-immunosuppressive medications that may contribute like PPI, H2 blockers, and oral hypoglycemics
3- first-line microbiological testing including PCR for C Diff, CMV, and multiplex
4- Second microbiological testing: stool PCR for viral pathogen, ova, and parasite evaluation; giardia and cryptosporidium enzyme immunoassay; and breath test for bacterial overgrowth.
3. What is the most likely explanation for this patient’s diarrhoea?
sapovirus infection resulting in acute worsening of chronic diarrhea 4. How should this patient be managed?
This patient was managed with intravenous fluids and reduction of MMF
Other:
GVHD, PTLD, IBD, Colon cancer, Malabsorption. What should be included in the diagnostic evaluation of posttransplant diarrhoea?
First we need to stop any non immunosuppressive medications that may cause diarrhea—such as proton pump inhibitors, H2 agonists, and oral hypoglycemic.
First-line microbiological testing including Clostridium difficile polymerase chain reaction (PCR),
CMV PCR, and multiplex PCR if available.
If above test negative second testing should include stool PCR for viral pathogen, ova, and parasite evaluation; giardia and cryptosporidium enzyme immunoassay; and breath test for bacterial overgrowth.
In this patient, tacrolimus level was found to be within desired therapeutic limits (7 ng/mL) and first line microbiological testing was negative.
Stool ova and parasite and stool culture were also negative.
Fecal multiplex PCR was positive for sapovirus What is the most likely explanation for this patient’s diarrhoea?
Sapovirus infection. How should this patient be managed
Intravenous fluid
Antimotility agent- loperamide
Reduction of immunosuppression
Close monitoring of the tacrolimus level
Limited data on Nitazoxanide
The diagnostic evaluation of post-transplant diarrhoea should include:
Stopping any non-immunosuppressive medications that may cause diarrhea as proton pump inhibitors, H2 agonists and oral hypoglycemics.
First-line microbiological testing including Clostridium difficile polymerase chain reaction (PCR), CMV PCR, and multiplex PCR if available.
Stool PCR for viral pathogen, ova, and parasite evaluation; giardia and cryptosporidium enzyme immunoassay; and breath test for bacterial overgrowth.
Colonoscopy and biopsy may be needed in some situations.
The most likely explanation for this patient’s diarrhoea
Is confirmed by positive stool PCR for Sapovirus infection resulting in acute worsening of chronic diarrhea.
Management should be:
Symptom relief with intravenous fluids for volume repletion and antimotility agents such as loperamide.
Reduction of immunosuppression especially the antimetabolite mycophenolate dosage.
Tacrolimus levels should be closely monitored.
Nitazoxanide can be tried as it is an antimicrobial agent with an antiviral effect by activating natural antiviral defenses and inhibiting cellular replication pathways.
Follow up for the patient’s appetite, weight gain, volume status, renal functions on frequent basis.
What should be included in the diagnostic evaluation of posttransplant diarrhoea?
– stop any non-immunosuppressive drugs that may cause diarrhoea e.g., PPIs, oral hypoglycemic agents, H₂ agonists
– 1st line microbiological tests i.e., serum/ blood CMV PCR/ NAT, stool C. difficile PCR, stool multiplex PCR, stool bacterial culture or PCR for bacterial pathogen
– if negative, proceed to 2nd tier microbiological tests i.e., evaluate for stool ova and parasites, stool viral PCR, stool giardia and cryptosporidium enzyme immunoassay (EIA), breath test for bacterial overgrowth
– if all the above are still negative, suspect other etiologies like malabsorption, PTLD, IBD consider doing OGD and colonoscopy with biopsy
What is the most likely explanation for this patient’s diarrhoea?
– sapovirus infection (detected in the fecal multiplex PCR ) causing an acute worsening of chronic diarrhoea
– this resulted in AKI due to volume depletion
– sapovirus infection has been associated with chronic, severe diarrhoea in kidney transplant recipients
How should this patient be managed?
– Tacrolimus trough level 7ng/mL
– 1st tier microbiological tests were negative (serum/ blood CMV PCR, stool C. difficile PCR, stool bacterial culture or stool bacterial PCR), stool ova and parasite, stool culture were also negative but fecal multiplex PCR was positive for sapovirus
– currently there are no therapies that have been shown to be effective in treating sapovirus infections
– hydration (IVF), antimotility drugs (e.g., loperamide), reduction in immunosuppression to promote the immune system to clear the viral infection
– enterocyte damage can disrupt the P-glycoprotein efflux pump leading to increased tacrolimus levels, hence monitor tacrolimus trough levels closely
– nitazoxanide has also been used with limited evidence (case reports), it is an antimicrobial agent which activates the natural antiviral defenses and inhibits the cellular pathways which lead to viral replication
– reduction in mycophenolate is a common practice, it has some efficacy in patients with persistent diarrhoea regardless of the cause
– caution should be observed since reduction in MPA dose may result in rejection and decreased graft survival
– the other option is switching from MMF to enteric coated mycophenolate or azathioprine since both of them are associated with a lower risk of developing posttransplant diarrhoea
– management of our case: IV hydration, reduction in immunosuppression (mycophenolate 720mg BD to 360mg BD)
– by day 3, the serum creatinine had normalized, the diarrhoea had subsided
– during his follow up, by week 3, there was significant clinical improvement, there was a complete resolution of the diarrhoea, with a 2-3kg weight gain
1. What is the differential diagnosis of diarrhoea following solid organ transplantation? · Diarrhea is a frequent complication after transplantation, with 3-year posttransplant cumulative incidence reported to be around 22%.
· The most common causes of diarrhea in patients after transplantation include infections, immunosuppressive medications, and antibiotics. · Noninfectious diarrhea in patients after transplantation is commonly due to immunosuppressive drugs, with the highest incidence associated with mycophenolic acid.Notably, patients with combined kidney-pancreas transplants are at a greater risk for rejection and thus have higher exposure to immunosuppression compared to those with other solid organ transplants.
· Infectious diarrhea following kidney transplantation is frequently attributed to Clostridium difficile, CMV, and norovirus.
2. What should be included in the diagnostic evaluation of posttransplant diarrhoea? · start with stopping any nonimmunosuppressive medications that may cause diarrhea—such as proton pump inhibitors, H2 agonists, and oral hypoglycemics—and first-line microbiological testing including Clostridium difficile polymerase chain reaction (PCR), CMV PCR, and multiplex PCR if available.
· If these tests return negative results, second-tier microbiological testing should include stool PCR for viral pathogen, ova, and parasite evaluation; giardia and cryptosporidium enzyme immunoassay; and breath test for bacterial overgrowth.
· In this patient, tacrolimus level was found to be within desired therapeutic limits (7 ng/mL) and first[1]line microbiological testing was negative.
· Stool ova and parasite and stool culture were also negative.
· Fecal multiplex PCR was positive for sapovirus
3. What is the most likely explanation for this patient’s diarrhoea? · Given the positive stool PCR, the most likely diagnosis is sapovirus infection resulting in acute worsening of chronic diarrhea. · Several recent case reports have described sapovirus infections leading to chronic, severe diarrhea in patients after kidney transplant. The prevalence of posttransplant sapovirus is unknown. · Diagnosis is typically made via real-time PCR or multiplex PCR testing of a stool sample.
4. How should this patient be managed? · To date there have been no therapies shown to be effective in treating sapovirus infections. · Previous reports have demonstrated symptom relief with intravenous fluids,antimotility agents such as loperamide, and reduction of immunosuppression to promote the immune system to clear the viral infection.
· In addition,tacrolimus levels should be closely monitored, as enterocyte damage can disrupt the P-glycoprotein efflux pump, leading to increased serum tacrolimus levels.
· Limited case studies have also suggested nitazoxanide as a potential therapeutic agent.
· Nitazoxanide is an antimicrobial agent that exerts its effect on viruses by activating natural antiviral defenses and inhibiting cellular pathways leading to viral replication. but Currently, evidence for its efficacy is limited to case reports.
· This patient was managed with intravenous fluids and reduction of his mycophenolate dosage from 720 mg twice a day to 360 mg twice a day.
· By hospital day 3, his serum creatinine had returned to baseline with interval improvement of acute diarrhea.
· At 3 weeks follow-up, the patient showed marked clinical improvement, with 2 to 3 kg of weight gain and complete resolution of his acute-on-chronic diarrhea.
· Reducing mycophenolate dosage in response to post[1]transplant diarrhea is a common practice and has been shown to have some efficacy in patients with persistent diarrhea regardless of cause.
· However, caution should be used when opting for this treatment strategy, as reductions in mycophenolate dose have also been shown to be associated with rejection and decreased allograft survival. Other possible treatment options include switching mycophenolic acid to an enteric-coated mycophenolate or azathioprine, both of which have been associated with a lower risk of developing posttransplant diarrhea.
Diarrhea in a Patient With Combined Kidney- Pancreas Transplant
Q1- What is the differential diagnosis of diarrhoea following solid organ transplantation?
Causes:
Simply classified in to two group :
either infectious or none infectious .
1- Infectious etiology : ( common cause are CMV and Clostridium difficile)
Q2- What should be included in the diagnostic evaluation of posttransplant diarrhoea?
History : should include
onset,
durations
associated symptoms ( fever, weight loss, relationship to meals, any blood in the stool, upper GIT manifestations and family history of same condition )
determine the offending drug and if it possible stop it : PPI , H2 agonists, Oral hypoglycemic agents .
Examination: for sign of dehydration, signs of infection , or lymphadenopathy, hepatosplenomegaly, skin rash.
Investigations :
GSE , stool for c/s . , CMV PCR.
Stool for C.difficile antigen & PCR , Clostridium difficile (PCR).
Stool for biofire for both bacteria and viruses .
Blood cultures and sensitivity.
Modified ZN stain for cryptosporidium.
Invasive – Colonoscopy
Breath test for bacterial overgrowth
Q3 What is the most likely explanation for this patient’s diarrhoea?
Most likely explanation is :
· presentation – chronic diarrhea and significant weight loss .
· positive for sapovirus by PCR may suggest the cause ·
. invasive CMV .
Q4 How should this patient be managed?
– No specific effective drug for sapovirus infections , but some studies suggested nitazoxanide as a potential therapeutic option.
– Supportive therapy: IV fluids , antimotility , and manipulation of immunosuppression- step wise reduction ·
– The index case is treated by intravenous fluids and reduction of immunosuppressive drug , with good response .
What is the differential diagnosis of diarrhea following solid organ transplantation?
Diarrhea post kidney transplant is common complications and has many causes such as infectious and non-infectious which is mainly related to immunosuppression medications or other drugs induced diarrhea.
D.D:
Infectious causes such as :bacterial, viral, and parasitic causes.
Non-infectious causes such as : Immunosuppressive medications, non-immunosuppressive medications and others (GVHD, PTLD, IBD, Colon cancer, and Malabsorption) , What should be included in the diagnostic evaluation of posttransplant diarrhea?
Microbiological testing including Clostridium difficile polymerase chain reaction
(PCR), CMV PCR, and multiplex PCR if available .
Stool PCR for viral pathogen, ova, and parasite evaluation; giardia and cryptosporidium enzyme immunoassay; and breath test for bacterial overgrowth • What is the most likely explanation for this patient’s diarrhea?
Infectious cause of diarrhea as multiplex PCR was positive for sapovirus which led to worsening of chronic diarrhea. • How should this patient be managed?
1-Intravenous fluids for adequate hydration.
2-Antimotility agents such as loperamide.
3-Reduction of immunosuppression to promote the immune system to clear the viral infection.
4-Nitazoxanide is an antimicrobial agent that exerts its effect on viruses.
5-Close monitoring of tacrolimus.
What should be included in the diagnostic evaluation of posttransplant diarrhoea? 1.Stopping any nonimmunosuppressive medications that may cause diarrhea. such as proton pump inhibitors, H2 agonists, and oral hypoglycemic.
3-Second-line microbiological testing; Including; stool PCR for viral pathogen, ova, and parasite evaluation; giardia and cryptosporidium enzyme immunoassay; and breath test for bacterial overgrowth. Than EGD, Colonoscopy with biopsy.
What is the most likely explanation for this patient’s diarrhoea? Fecal multiplex PCR was positive for sapovirus infection causing acute worsening of chronic diarrhea.
How should this patient be managed? There is no definitive therapies shown to be effective in treating sapovirus infections. –Oral hydration if not tolerated iv hydration –Reduce the dose of EC-MMF to 360mg BID. –Monitor of Tacrolimus level. –Kidney function test monitoring because of reduction in MMF. –Antimotility agents such as loperamide can be given once infection is excluded. –Limited case studies have also suggested Nitazoxanide as a potential therapeutic agent.
What should be included in the diagnostic evaluation of posttransplant diarrhoea1- stop non immunosuppressive medications if diarrhea persist:
2- do test on stool examination for clostridium difficile and bacterial overgrowth if diarrhea persist and test are negative
3-multiplex PCR of stool sample on various pathogens
3- do CMV PCR if negative
4-manipulate immunosuppressive medications guided by trough levels and TDM
What is the most likely explanation for this patient’s diarrhoea
Sapoviruses recent infection?? confirmed by PCR multiplex on stool sample
How should this patient be managed1- hospitalization and supportive treatment iv fluids
2- decrease dose of myfortic
3-antimotility and antimicrobial drugs
1-What is the differential diagnosis of diarrhoea following solid organ transplantation. Infectious : Bacteria ;
Clostridium difficile Campylobacter spp. Salmonella spp.
Bacterial overgrowth Aeromonas spp. Escherichia coli Viruses ;
CMV Norovirus Sapovirus
Rotavirus Adenovirus Enterovirus Parasitic ;
Giardia Cryptosporidium Isospora , Cyclospora Microsporidium Entamoeba Noninfectious : Immunosuppressive medications ;
Mycophenolate Tacrolimus Cyclosporine Sirolimus Nonimmunosuppressive medications;
Antibacterial Antiarrhythmic Antidiabetic Laxatives
Proton pump inhibitors Protease inhibitors Others ;
GVHD PTLD IBD Colon cancer Malabsorption 2-What should be included in the diagnostic evaluation of posttransplant diarrhoea?
1-Stopping any nonimmunosuppressive medications that may cause diarrhea;
such as proton pump inhibitors, H2 agonists, and oral hypoglycemic.
2-First-line microbiological testing;
Including; Clostridium difficile polymerase chain reaction (PCR), CMV PCR, and multiplex PCR if available.
-If these tests return negative results,
3-Second-line microbiological testing;
Including; stool PCR for viral pathogen, ova, and parasite evaluation; giardia and cryptosporidium enzyme immunoassay; and breath test for bacterial overgrowth. 3-What is the most likely explanation for this patient’s diarrhoea?
-Fecal multiplex PCR was positive for sapovirus;(nonenveloped, single-stranded positive-sense RNA viruses that belong to the Caliciviridae family along with norovirus).
-The most likely diagnosis is sapovirus infection resulting in acute worsening of chronic diarrhea. 4-How should this patient be managed? –To date, there is no therapies shown to be effective in treating sapovirus infections. –As pt is hemodynamically stable and no vomiting to encourage him for good oral hydration, but if has vomiting and hemodynamically unstable intravenous fluid should be started. –Reduce the dose of EC-MMF to 360mg BID. –Close monitoring of Tacrolimus level. –Close kidney function test because of reduction in MMF. –Antimotility agents such as loperamide can be given after R/O infective causes. –Limited case studies have also suggested Nitazoxanide as a potential therapeutic agent.
Diarrhoea in a Patient with Combined Kidney-Pancreas Transplant
1. What is the differential diagnosis of diarrhoea following solid organ transplantation? 2. What should be included in the diagnostic evaluation of posttransplant diarrhoea? 3. What is the most likely explanation for this patient’s diarrhoea? 4. How should this patient be managed?
The differential diagnosis of diarrhea following solid organ transplantation includes:
Diarrhea is one of the most common complaints in post-transplant. Almost 25% of recipients develop diarrhea which disturbs their quality of life.
Infectious Causes:
Bacterial:
Clostridium difficile E. coli Campylobacter jejunii Salmonella species Bacterial overgrowth syndrome Aeromonas species Tuberculous colitis Viral:
Colon cancer GVHD Inflammatory bowel disease Malabsorption syndromes What should be included in the diagnostic evaluation of posttransplant diarrhoea?
Detailed history should be taken about onset, course and durations of diarrhea and if there are any symptoms of infection like fever, weight loss, relationship to meals, any blood in the stool, upper GIT manifestations and any other family member developed same picture.
Examination: looking for any signs of infection or malignancy lymphadenopathy, hepatosplenomegaly
Laboratory investigations:
Stool microscopy and culture The Common Tests to be done; Clostridium difficile polymerase chain reaction (PCR), CMV PCR. Stool for C.difficile antigen and PCR Stool for biofire for both bacteria and viruses CMV PCR Blood cultures Modified ZN stain for cryptosporidium. Colonoscopy – To assess for colitis. Breath test for bacterial overgrowth
·
What is the most likely explanation for this patient’s diarrhoea?
The patient had a positive stool test for sapovirus – so that was the cause of the diarrhea, which can be diagnosed by real-time PCR or multiplex PCR testing of stool samples. However, the patient is also on enteric coated mycophenolate sodium at 720 mg twice daily – although it is the enteric coated mycophenolate sodium and not the mycophenolate mofetil – it can also cause diarrhea and it is at a high dose three years post-transplant.
How should this patient be managed?
If your patients with symptoms and signs of Effective arterial blood volume depletion (JVP, Chest, LL edema, Orthostatic changes….) , History of previous AKI you should start managing with;
Intravenous fluids, UOP chart. Reduction of immunosuppression to promote the immune system. Reduce the dose of the EC-mycophenolate sodium to 360 mg BD while closely monitoring the graft function. Other possible treatment options include switching of immunosuppressant. He is already on enteric-coated mycophenolate so I may need to shift to azathioprine, both of which have been associated with a lower risk of developing post-transplant diarrhea. Not many patients benefit from conversion conversion of MMF to myfortic. Please change to azathioprine or to a smaller dose sirolimus as an adjunct if that patient cannot be giving azathioprine to avoid interaction with allopurinol. Tacrolimus levels should also be monitored, as enterocyte damage can disrupt the P-glycoprotein efflux pump. Monitor the tacrolimus levels and mycophendlate levels as enterocyte damage due to the chronic diarrhea can cause increased absorption and toxicity. Nitazoxanide is an antimicrobial agent that exerts its effect on viruses by activating natural antiviral defenses and inhibiting cellular pathways leading to viral replication. Antimotility agents such as loperamide after exclusion of infectious causes,
The differential diagnosis of diarrhea following solid organ transplantation includes: Infectious Causes: Bacterial:
Clostridium difficile
E.coli
Campylobacter jejunii
Salmonella species
Bacterial overgrowth syndrome
Aeromonas species
Tuberculous colitis
Viral:
CMV
Norovirus
Sapovirus
Adenovirus
Enterovirus
Parasites:
Giardia lamblia
Cryptosporidium parvum
Microsporidioisis
Isosporal belli
Entameba histolytic
Non-Infectious Drugs: Immunosuppressants:
Mycophenolate mofetil
Tacrolimus
Cyclosporine
Sirolimus
Non-immunosuppressants:
Antimicrobials
Proton pump inhibitors
H2 receptor antagonists
Laxatives
ARVs – protease inhibitors
Antiarrhythmics Other Causes:
Colon cancer
GVHD
Inflammatory bowel disease
Malabsorption syndromes
Diagnostic Evaluation:
Detailed history: Duration of symptoms, drug history, associated symptoms like fever, weight loss, relationship to meals, any blood in the stool
Examination: lymphadenopathy, hepatosplenomegally
Laboratory investigations:
Stool microscopy and culture
Stool for C.difficile antigen and PCR
Stool for biofire for both bacteria and viruses
CMV PCR
Blood cultures
Modified ZN stain for cryptosporidium
Colonoscopy – To assess for colitis
Breath test for bacterial overgrowth
Likely explanation for the patients diarrhea:
The patient had a positive stool test for sapovirus – so that was the cause of the diarrhea
However, the patient is also on enteric coated mycophendlate sodium at 720 mg twice daily – although it is the enteric coated mycophendlate sodium and not the mycophendlate mofetil – it can also cause diarrhea and it is at a high dose three years post-transplant
Management:
Adequate hydration using oral and IV fluids
Strict fluid input output monitoring
Monitor the tacrolimus levels and mycophendlate levels as enterocyte damage due to the chronic diarrhea can cause increased absorption and toxicity
Reduce the dose of the EC-mycophenolate sodium to 360 mg BD while closely monitoring the graft function
What should be included in the diagnostic evaluation of posttransplant diarrhoea?
Stool analysis for ova, and parasite evaluation, giardia gram stain , Stool culture ,PCR for viral, cryptosporidium enzyme immunoassay, and breath test for bacterial overgrowth.
What is the most likely explanation for this patient’s diarrhoea?
The most likely cause of chronic diarrhea in patients after kidney transplant is sapovirus infection which can be diagnosed by real-time PCR or multiplex PCR testing of stool samples.
How should this patient be managed?
The patient should be assessed regarding symptoms and signs of dehydration but he is already having frequent motions with AKI so I will start managing
Intravenous fluids,
Antimotility agents such as loperamide after exclusion of infectious causes ,
Reduction of immunosuppression to promote the immune system.
Tacrolimus levels should also be monitored, as enterocyte damage can disrupt the P-glycoprotein efflux pump.
Nitazoxanide is an antimicrobial agent that exerts its effect on viruses by activating natural antiviral defenses and inhibiting cellular pathways leading to viral replication.
Other possible treatment options include switching of immunosuppressant . He is already on enteric-coated mycophenolate so I may need to shift to azathioprine, both of which have been associated with a lower risk of developing post transplant diarrhea.
What is the differential diagnosis of diarrhea following solid organ transplantation?
– Infectious
o Bacteria
Clostridium difficile.
Campylobacter spp.
Salmonella spp.
Bacterial overgrowth.
Aeromonas spp.
Escherichia coli.
o Viruses
CMV.
Norovirus
Sapovirus
Rotavirus.
Adenovirus.
Enterovirus.
o Parasitic
Giardia
Cryptosporidium
Isospora, Cyclospora
Microsporidium.
Entamoeba
– Noninfectious
o Immunosuppressive medications.
Mycophenolate.
Tacrolimus.
Cyclosporine.
Sirolimus. o Nonimmunosuppressive medications.
Antibacterial
Antiarrhythmic
Antidiabetic
Laxatives
Proton pump inhibitors
Protease inhibitors. o Other
GVHD
PTLD
IBD
Colon cancer
Malabsorption What should be included in the diagnostic evaluation of posttransplant diarrhea?
· It is critical to stop any nonimmunosuppressive medications that may cause diarrhea—such as
o Proton pump inhibitors,
o H2 agonists,
o Oral hypoglycemic
· First-line microbiological testing including
o Clostridium difficile polymerase chain reaction (PCR),
o CMV PCR,
o Multiplex PCR if available
· If these tests return negative results, second-tier microbiological testing should include:
o Stool PCR for the viral pathogen, ova, and parasite evaluation; giardia and cryptosporidium enzyme immunoassay;
o Breath test for bacterial overgrowth.
· EGD, Colonoscopy with biopsy.
What is the most likely explanation for this patient’s diarrhea?
Given the positive stool PCR, sapovirus infection, which causes sudden exacerbation of chronic diarrhea, is the most likely diagnosis.
How should this patient be managed?
There are currently no treatments that have been demonstrated to be successful in treating sapovirus infections.
Past studies have shown that:
• Intravenous fluids, antimotility medications such loperamide,
• Immunosuppression should be reduced to encourage the immune system to fight off the viral infection.
• It is important to closely monitor tacrolimus levels because enterocyte injury can impair the P-glycoprotein efflux pump, which raises the concentration of tacrolimus in the blood.
• Nitazoxanide has also been mentioned as a potential therapeutic drug in a few case reports.
• Patients with persistent diarrhea, regardless of the etiology, may benefit from reducing their mycophenolate dosage as a reaction to posttransplant diarrhea.
1.What is the differential diagnosis of diarrhoea following solid organ transplantation?Diarrhoea in the post transplant can be divided into infectious and non-infectious causes.
Non-infectious causes are mainly attributed to drugs and they include:
Immunosuppressive- MMF most commonly, others tacrolimus, sirolimus
Infectious causes: Most infectious causes in the post-transplant is CMV.
Bacterial- C.difficile, campylobacter, salmonella
Viral- noravirus, rotavirus, adenovirus, CMV
Parasitic- giardia, cryptosporidium, entamoeba
• Other causes:
GVHD
PTLD
IBD
Colon cancer
Malabsorption
What should be included in the diagnostic evaluation of post-transplant diarrhoea?Current guidelines for evaluation of diarrhoea in solid-organ transplant recipients from the Infectious Disease Community of Practice of the American Society of Transplantation state:
First tier microbiological testing:
C.difficile PCR in stool
CMV qPCR/NAT in serum/blood
Bacterial culture or PCR for bacterial pathogen(stool)
Multiplex PCR if available.
Second tier microbiological testing:
Viral PCR in stool
Ova and parasite evaluation in stool
Giardia and cryptosporidium EIA in stool.
Breath test for bacterial overgrowth.
Colonoscopy with biopsy may be considered as a final step.
What is the most likely explanation for this patient’s diarrhoea?Sapovirus
How should this patient be managed?Reduction of immunosuppressive agents to allow the immune system to clear the virus.
Reduction of the MMF dose or switching to EC-MPS
Close monitoring of the tacrolimus trough levels, the enterocyte damage can disrupt p-glycoprotein efflux pump leading to increased tacrolimus levels.
Nitazoxide has potential therapeutic potential, though evidence of its use is limited to case reports.
Other treatment options: use of anti motility agents- loperamide, IVF rehydration.
Ø Differential diagnosis of diarrhea post transplantation:
· Infectious diarrhea (viral as CMV, norovirus, rotavirus, adenovirus), bacterial (Cl-difficile, salmonella, E coli, campylobacter), protozoa (cryptosporidium, giardia and microsporidia). While most common are CMV, cl-difficle and Norovirus.
· Drug induced (IS as MMF and CNI), others as PPI, laxatives and prolonged use of antimicrobial.
· Other disorders as duodenal villous atrophy, IBD like and GVHD.
Ø What should be included in diagnostic evaluation of diarrhea post transplantation:
· Step wise approach is used.
· Stop any non immunosuppressive drugs as PPI, H2 agonists and oral hypoglycemics.
· Then test for Clostridium difficile PCR, CMV PCR, and multiplex PCR if available.
· If above-mentioned tests are -ve, proceed to stool PCR for viral pathogen, ova, and parasite evaluation; giardia and cryptosporidium enzyme immunoassay; and breath test for bacterial overgrowth.
Ø Most likely explanation of index case:
· The index case is presented with chronic diarrhea and significant weight loss.
· Fecal multiplex PCR was positive for sapovirus which suggests that it is the cause of worsening diarrhea.
· Note that, he has high risk for CMV infection due serological status (D+/R-), plus over immunosuppression used in cases with combined kidney and pancreas transplantation (as they have very high risk of AR), but here CMV PCR ids negative (it can be -ve in 15 % of cases with CMV tissue invasive disease and diagnosis requires endoscopy and tissue biopsy).
Ø Treatment of the index case:
o No specific anti-viral therapy is available.
o Just supportive therapy with intravenous fluids, antimotility agents such as loperamide, and reduction of immunosuppression (especially MMF or shift to EC-MPS or AZA), but with caution and close monitoring of the graft function to guard against AR.
o Nitazoxanide is an antimicrobial with ? antiviral properties and inhibit cellular pathways required for viral replication.
Why mention IV fluids to begin with in everyone with post transplant diarrhoea? My caution: antimotility agents such as loperamide ONLY after excluding infectious cause . Not many patient benefit from conversion conversion of MMF to myfortic. Please change to azathioprine or to a smaller dose sirolimus as an adjunct if that patient can not be give azathioprine to avoid interaction with allopurinol.
1.What is the differential diagnosis of diarrhoea following solid organ transplantation?
Infections, IS drugs, & antibiotics are the most frequent causes of diarrhea post SOT.
IS medications frequently cause non-infectious diarrhea in SOT recipients, with mycophenolic acid having the highest prevalence.
Compared to recipients of other SOT, patients with combined kidney-pancreas TX are more likely to have immunosuppression due to a higher risk of rejection.
The common causes of infectious diarrhea after KTX are Clostridium difficile, CMV, & norovirus. =========================== 2.What should be included in the diagnostic evaluation of posttransplant diarrhea? Determining the origin of diarrhea, since pinpointing the source can enable targeted treatment. Stopping any non-immunosuppressive medications that may cause diarrhea—such as PPIs, H2 agonists, diuretics, & oral hypoglycemic 1st-line microbiological testing (CDI PCR, CMV PCR, & multiplex PCR, if available). 2nd-tier microbiological testing should consist of stool PCR for the viral pathogens, ova, & parasites, giardia & cryptosporidium enzyme immunoassay, and breath test for bacterial overgrowth if 1st tier tests yield negative results. =========================== 3.What is the most likely explanation for this patient’s diarrhoea?
Tacrolimus levels in this patient were within the targeted therapeutic range (7 ng/mL), & initial microbiological testing came out negative.
The stool culture, stool ova, & stool parasite tests were all negative.
Fecal multiplex PCR detected sapovirus. Hence, sapovirus infection causing an acute exacerbation of chronic diarrhea is the most likely diagnosis.
Along with norovirus, sapoviruses are members of the Caliciviridae family of ss RNA viruses.
One multiplex PCR assay checks for a range of stool pathogens, including viruses, bacteria, & parasites including Cryptosporidium, Cyclospora cayetanensis, Entamoeba histolytica, & Giardia lamblia. =========================== 4.How should this patient be managed?
No specific therapy for sapovirus.
Treatment is supportive with IV fluids, antimotility agents (loperamide), & reduction of IS medications to promote the immune system to clear the viral infection.
Regular monitor of tacrolimus levels because enterocyte damage can impair the P-glycoprotein efflux pump, which raises the tacrolimus blood levels.
Reduction of MMF dosage from 720 mg twice a day to 360 mg twice a day. Caution should be used as reductions
in MMF are associated with rejection & reduced graft survival.
Changing from MMF to an EC-MPS or AZA, both of which have been linked to a lower risk of developing diarrhea, are further therapeutic choices.
Why mention IV fluids to begin with in everyone with post transplant diarrhoea? My caution: antimotility agents such as loperamide ONLY after excluding infectious cause .
What is the differential diagnosis of diarrhoea following solid organ transplantation?
Infectious: •Bacteria B Clostridium difficile B Campylobacter spp. B Salmonella spp. B Bacterial overgrowth B Aeromonas spp. B Escherichia coli •Viruses B CMV B Norovirus B Sapovirus B Rotavirus B Adenovirus B Enterovirus •Parasitic B Giardia B Cryptosporidium B Isospora, Cyclospora B Microsporidium B Entamoeba Noninfectious.
What should be included in the diagnostic evaluation of posttransplant diarrhoea? Current guidelines for evaluation of diarrhea in solid-organ transplant recipients from the Infectious Disease Community of Practice of the American Society of Transplantation:
(1) Stop non-immunosuppressive medications causing diarrhea, example PPI. (2) Microbilogical tresting: – Clostridium difficile polymerase chain reaction (PCR), CMV PCR, and multiplex PCR if available. – microbiological testing should include stool PCR for viral pathogen, ova, and parasite evaluation; giardia and cryptosporidium enzyme immunoassay; and breath test for bacterial overgrowth. (3) immunosuppressive manibulation – reducing the dose of MMF or shifting to EC-MPA ,or azathioprine.
What is the most likely explanation for this patient’s diarrhoea? By exclusion of the most common causes of infectious diarrhea C.difficle, CMV, and bacterial stool cultures, multiplex PCR might be of benefit. Positive stool PCR for sapovirus, causing acute on top of chronic diarrhea, with worsening kidney function. Sapovirus infections is a single stranded positive sense RNA virus (Caliciviridae family), can lead to chronic, severe diarrhea in patients after kidney transplant, and diagnosis is made via real-time PCR or multiplex PCR testing.
How should this patient be managed? IV hydration with isotonic solutions and correction of electrolytes derrangment. Antimotalilty – loperamide. Reduction of immunosupreesive medications, promoting immune system to eliminate the virus. Reducing MMF dose by 50% (but might increase the risk of rejection), so switching to EC-MPA, or azathioprine may be beneficial and protect against rejection. Close monitoring of tacrolimus level, to keep therapeutic level with close monitoring of graft function. Nitazoxanide is an antimicrobial agent poses anti-viral activity by energizing cellular pathways that support viral replication and natural antiviral defenses, in case reports only.
Why mention IV fluids to begin with in everyone with post transplant diarrhoea? My caution: antimotility agents such as loperamide ONLY after excluding infectious cause .
In transplant patients, diarrhea is frequent. While the majority of cases are minor and short-lived, some are serious and persistent, which puts graft at risk by causing dehydration, so preemptive iv crystalloid may be helpfull, with correction of electrolytes.
diarrhea cause normal anion gap acidosis which may be resposive to iv fluids and isotonic bicarbonate
Diarrhea is one of the most common complaints in post-transplant. Almost 25% of recipients develop diarrhea which disturbs their quality of life.
Causes of post-transplant diarrhea
A- Infectious diarrhea
Bacteria such as clostridium deficile, salmonella, shigella, E coli, and bacterial overgrowth
Viruses such as SARS-cove 2, CMV, adenovirus, norovirus, rotavirus
Parasites such as giardiasis, entamoeba histolotica, cryptosporidium
B-Non-infectious diarrhea
· Drug induced: MMF, CNI, sirolimus, antibiotics, proton pump inhibitors
· Malignancy such as cancer colon, PTLD How to approach:
The main important issue is to differentiate between infectious causes from noninfectious causes
1- detailed history should be taken about onset, course and durations of diarrhea and if there is any symptoms of infection like fever, upper GIT manifestations and any other family member developed same picture.
2- Examination: looking for any signs of infection or malignancy
3- Investigations include:
· Primary investigations including CNI level, CMV PCR, Stool culture and CD toxin in stool
· Secondary investigations (if primary investigations were not conclusive) including stool multiplex PCR for viral, bacterial and parasitic infection (Cryptosporidium, Entamoeba histolytica, Giardia lamblia, Campylobacter, Shigella, Salmonella, Vibrio, Yersinia enterocolitica, adenovirus and sapovirus), enzyme immunoassay for giardia and cryptosporidium and breath test for bacterial overgrowth
· Imaging, colonoscopy, and biopsy may be needed if there is suspicious of malignancy or CMV colitis with negative PCR Current guidelines for evaluation of diarrhea in solid-organ transplant recipients from the Infectious Disease Community of Practice of the American Society of Transplantation:
1. stopping any medications of non-immunosuppressive medications if possible.
2. Monitor CNI level and keep it on the lower level.
3. first-line microbiological testing including Clostridium difficile polymerase chain reaction (PCR), CMV PCR, and multiplex PCR if available.
4. Colonoscopy for detection of CMV tissue invasion with negative PCR and PTLD.
5. second-tier microbiological testing should include stool PCR for viral pathogen, ova, and parasite evaluation; giardia and cryptosporidium enzyme immunoassay; and breath test for bacterial overgrowth. What is the most likely explanation for this patient’s diarrhoea?
Sapoviruses.
How should this patient be managed?
1- Supportive therapy including intravenous fluids and correction of electrolytes disturbances
2- Symptomatic therapy including loperamide to decrease bowel motions
3- Modulation and monitoring of immunosuppression
· keeping CNI trough level at lower level.
· Shifting to enteric coated mycophenolate maybe beneficial.
· Close follow up of CNI level with possible of increase of the level because diarrhea associated with damage of P-glycoprotein.
4- Nitazoxanide can be used due to its antiviral effect.
1. What is the differential diagnosis of diarrhoea following solid organ transplantation? The most common causes of diarrhea in patients after transplantation include:
· Infectious diarrhea: infections; frequently attributed to Clostridium difficile, CMV, and norovirus.
· Non-infectious diarrhea as a result of immunosuppressive medications, with the highest incidence associated with mycophenolic acid
· Antibiotics. 2. What should be included in the diagnostic evaluation of posttransplant diarrhoea? It is critical to evaluate the cause of diarrhea in a kidney transplant recipient, as identification of a specific etiology may allow for a focused treatment. Current guidelines for evaluation of diarrhea in solid-organ transplant recipients from the Infectious Disease Community of Practice of the American Society of Transplantation recommend:
· Start with stopping any non-immunosuppressive medications that may cause diarrhea—such as proton pump inhibitors, H2 agonists, and oral hypoglycemics
· first-line microbiological testing including Clostridium difficile polymerase chain reaction (PCR), CMV PCR, and multiplex PCR if available.
· If these tests return negative results, second microbiological testing should include stool PCR for viral pathogen, ova, and parasite evaluation; giardia and cryptosporidium enzyme immunoassay; and breath test for bacterial overgrowth.
3. What is the most likely explanation for this patient’s diarrhoea? For this patient, tacrolimus level was found to be within desired therapeutic limits (7 ng/mL) and first line microbiological testing was negative. Stool ova and parasite and stool culture were also negative. Fecal multiplex PCR was positive for sapovirus infection. 4. How should this patient be managed?
· To date there have been no therapies shown to be effective in treating sapovirus infections.
· Previous reports have demonstrated symptom relief with intravenous fluids, antimotility agents such as loperamide, and reduction of immunosuppression to promote the immune system to clear the viral infection.
· Limited case studies have also suggested nitazoxanide as a potential therapeutic agent.
· This patient was managed with intravenous fluids and reduction of his mycophenolate dosage from 720 mg twice a day to 360 mg twice a day. This was associated with improvement of acute diarrhea and complete resolution of his acute-on-chronic diarrhea.
Why mention IV fluids to begin with in everyone with post transplant diarrhoea? My caution: antimotility agents such as loperamide ONLY after excluding infectious cause . I like that your suggestion of monitoring tacrolimus levels closely.
Differential diagnosis of diarrhoea following solid organ transplantation?
Diarrhea is a common post-transplant problem, with a 3-year cumulative incidence reported to be around 22%.
It has been linked to worse clinical outcomes, such as acute kidney damage (AKI), tacrolimus and mycophenolate levels that are over therapeutic ranges, and lower graft and patient survival.
Those who have undergone transplantation are most frequently affected by infections, immunosuppressive drugs, and antibiotics for diarrhea.
Immunosuppressive medications frequently cause non-infectious diarrhea in transplant recipients, with mycophenolic acid having the highest prevalence.
Significantly, compared to recipients of other solid organ transplants, individuals with combined kidney-pancreas transplants are more likely to have immunosuppression due to a higher risk of rejection.
The common causes of infectious diarrhea after kidney donation are Clostridium difficile, CMV, and norovirus.
Diagnostic evaluation of posttransplant diarrhoea?
It is crucial to determine the root of diarrhea in kidney transplant recipients since pinpointing the source may enable targeted treatment.
Stopping any non-immunosuppressive drugs that may cause diarrhea is the first step in the current American Society of Transplantation guidelines for evaluating diarrhea in solid-organ transplant recipients.
STOP proton pump inhibitors, H2 agonists,and oral hypoglycemics—and first-line microbiological testing including Clostridium difficile polymerase chain reaction (PCR), CMV PCR, and multiplex PCR
Second-tier microbiological testing should include stool PCR for viral pathogen, ova, and parasite evaluation; giardia and cryptosporidium enzyme immunoassay; and breath test for
bacterial overgrowth
Likely explanation for this patient’s diarrhoea?
The most likely diagnosis, given the positive stool PCR, is sapovirus infection, which causes abrupt exacerbation of chronic diarrhea.
Recent case reports indicate sapovirus infections causing patients to experience chronic, severe diarrhea following kidney transplants.
Together with norovirus, sapoviruses are single-stranded positive-sense RNA viruses that are not enclosed and do not belong to the Caliciviridae family.
Usually, a stool sample is tested using real-time PCR or multiplex PCR to make the diagnosis.
Patient management?
There are currently no treatments that have been demonstrated to be successful in treating sapovirus infections.
Past studies have shown that intravenous fluids, antimotility medications like loperamide, and a reduction in immunosuppression can all help relieve symptoms and encourage the immune system to fight off the viral infection.
Also, it’s important to keep an eye on tacrolimus levels since enterocyte damage can impair the P-glycoprotein efflux pump, which raises tacrolimus levels in the blood.
It is usual practice to reduce mycophenolate dosage in response to post-transplant diarrhea, and it has been demonstrated to be somewhat effective in patients with persistent diarrhea, regardless of the cause.
Why mention IV fluids to begin with in everyone with post transplant diarrhoea? My caution: antimotility agents such as loperamide ONLY after excluding infectious cause .
I would suggest careful monitoring tacrolimus levels closely.
What is the differential diagnosis of diarrhea following solid organ transplantation?
1. Infectious causes, including a) bacteria, such as Clostridium difficile, Campylobacter spp., Salmonella spp., bacterial overgrowth, Aeromonas spp., and Escherichia coli; b) viruses, such as Cytomegalovirus, Norovirus, Sapovirus, Rotavirus, Adenovirus, and Enterovirus; and c) parasites, such as Giardia, Crypto
Second, factors other than infections include: a) immunosuppressive drugs; B Immunosuppressive drugs: mycophenolate, tacrolimus, cyclosporine, and sirolimus Non-immunosuppressive drugs: antimicrobial, antiarrhythmic, anti-diabetic, laxative, proton pump inhibitor, and protease inhibitor are only a few examples.
Thirdly, besides GVHD, PTLD, and IBD, there are a few others: Colorectal cancer: malabsorption
What should be included in the diagnostic evaluation of posttransplant diarrhea?
Stool analysis and culture
Multiplex PCR testing of a stool sample for the viral pathogen, ova, and parasite evaluation; giardia and cryptosporidium enzyme immunoassay; and breath test for bacterial overgrowth.
putting an end to the use of non-immunosuppressive drugs, undergoing first-line microbiological testing, having a stool PCR done, as well as giardia and cryptosporidium enzyme immunoassays, and doing a breath test.
It was determined that the tacrolimus level was within the therapeutic limits, and the first-line microbiological tests came out negative.
A positive result for sapovirus was found in the fecal multiplex PCR.
CMV PCR.
What is the most likely explanation for this patient’s diarrhea?
This patient’s diarrhea is likely caused by a sapovirus infection.
Tacrolimus was within therapeutic limits.
Fecal multiplex PCR detected sapovirus. Stool ova, parasite, and culture were negative.
How should this patient be managed?
Sapovirus infections have no effective treatments. Intravenous fluids, loperamide, and immunosuppression lowering have been shown to relieve symptoms.
Intravenous fluids
F/U tacrolimus level
Nitazoxanide may potentially be a treatment.
reducing mycophenolate dose has been proven to help.
Switching to enteric-coated mycophenolate or azathioprine, which reduces posttransplant diarrhea risk, is another option.
Why mention IV fluids to begin with in everyone with post transplant diarrhoea?
My caution: antimotility agents such as loperamide ONLY after excluding infectious cause .
I like that your suggestion of monitoring tacrolimus levels closely.
IV fluids if the patient has a manifestation of dehydration and his oral intake can’t match the water deficit. we face these cases frequently(8-10 times per day) and the patient has AKI.
D- Others including graft versus host disease, IBD, malabsorption What should be included in the diagnostic evaluation of posttransplant diarrhoea?
Diagnostic work up should include
A- Routine investigations
Renal function tests and electrolytes
Complete blood count, c reactive protein
Stool analysis
B- Searching for the cause
Primary investigations including CNI level, CMV PCR, Stool culture and CD toxin in stool
Secondary investigations (if primary investigations were not conclusive) including stool multiplex PCR for viral, bacterial and parasitic infection (Cryptosporidium, Entamoeba histolytica, Giardia lamblia, Campylobacter, Shigella, Salmonella, Vibrio, Yersinia enterocolitica, adenovirus and sapovirus), enzyme immunoassay for giardia and cryptosporidium and breath test for bacterial overgrowth
Imaging, colonoscopy, and biopsy may be needed if there is suspicious of malignancy or CMV colitis with negative PCR
What is the most likely explanation for this patient’s diarrhoea?
Sapoviruses infection is the most likely diagnosis since it was detected by PCR, and no other cause was detected in the primary investigations
How should this patient be managed?
1- Supportive therapy including intravenous fluids for treatment of dehydration
2- Symptomatic therapy including lopramide to decrease bowel motions
3- Modulation and monitoring of immunosuppression
Reduction of immunosuppression in the form of reducing the dose of MMF after estimation of the rejection risk and keeping low target trough for CNI
Shifting to enteric coated mycophenolate or azathioprine is an option
Close follow up of CN level as there may be an increase in tacrolimus level with diarrhea due to disruption of P-glycoprotein efflux pump in the damaged enterocytes
4- Some experts recommend the use of nitazoxanide due to its antiviral effect, but the evidence is limited
What is the differential diagnosis of diarrhoea following solid organ transplantation? 1. Infectious causes:
a) Bacteria
· Clostridium difficile
· Campylobacter spp.
· Salmonella spp.
· Bacterial overgrowth
· Aeromonas spp.
· Escherichia coli
b) Viruses
· CMV
· Norovirus
· Sapovirus
· Rotavirus
· Adenovirus
· Enterovirus
c) Parasitic
· Giardia
· Cryptosporidium
· Isospora, Cyclospora
· Microsporidium
· Entamoeba 2. Non-infectious causes:
a) Immunosuppressive medications B Mycophenolate
· Tacrolimus
· Cyclosporine
· Sirolimus
b) Non-immunosuppressive medications
· Antibacterial
· Antiarrhythmic
· Antidiabetic
· Laxatives
· Proton pump inhibitors
· Protease inhibitors 3. Others:
· GVHD
· PTLD
· IBD
· Colon cancer
· Malabsorption
What should be included in the diagnostic evaluation of posttransplant diarrhoea?
1. Stopping any nonimmunosuppressive medications that may cause diarrhea.
2. Immunosuppression drug level.
3. first-line microbiological testing including Clostridium difficile polymerase chain reaction (PCR), CMV PCR, and multiplex PCR if available.
4. Second-tier microbiological testing should include stool PCR for viral pathogen, ova, and parasite evaluation; giardia and cryptosporidium enzyme immunoassay; and breath test for bacterial overgrowth.
What is the most likely explanation for this patient’s diarrhoea? Sapovirus infection is the most likely explanation for this patient’s diarrhoea.
· Tacrolimus level was found to be within desired therapeutic limits (7 ng/mL).
· First- line microbiological testing was negative.
· Stool ova and parasite and stool culture were negative.
· Fecal multiplex PCR was positive for sapovirus.
How should this patient be managed? 1. Adequate hydration. 2. Antimotility agents such as loperamide. 3. Reduction or modification of immunosuppression to promote the immune system to clear the viral infection. · Reducing mycophenolate dosage. · Switching mycophenolic acid to an enteric-coated mycophenolate or azathioprine. 4. Tacrolimus levels should be closely monitored, as enterocyte damage can disrupt the P-glycoprotein efflux pump, leading to increased serum tacrolimus levels. 5. Nitazoxanide is suggested as a potential therapeutic agent(its efficacy is limited to case reports).
No therapies have been shown to be effective in treating sapovirus infections, butintravenous fluids, antimotility agents, reduction of immunosuppression, tacrolimus levels should be monitored, and nitazoxanide may be a potential therapeutic agent.
Reducing mycophenolate dosage in response to post-transplant diarrhea has been shown to have some efficacy, but caution should be used.
This patient was managed with intravenous fluids and reduced mycophenolate dosage, and by hospital day 3, serum creatinine had returned to baseline with interval improvement of acute diarrhea.
What is the differential diagnosis of diarrhoea following solid organ transplantation?
The most common causes of diarrhea in patients after transplantation include infections, immunosuppressive medications, and antibiotics
Other GVHD, PTLD, IBD, colon cancer, malabsorption, microscopiccolitis, malakoplakia
What should be included in the diagnostic evaluation of posttransplant diarrhoea?o Start with stopping any nonimmunosuppressive medications that may cause diarrhea (proton pump inhibitors, H2 agonists, and oral hypoglycemic)
o First-line microbiological testing including Clostridium difficile PCR, CMV PCR, and multiplex PCR if available
o If these tests return negative, second-tier microbiological testing should include stool PCR for viral pathogen, ova, and parasite evaluation; giardia and cryptosporidium enzyme immunoassay; and breath test for bacterial overgrowth
What is the most likely explanation for this patient’s diarrhoea?o sapovirus infection (Fecal multiplex PCR was positive for sapovirus)
o Sapoviruses are nonenveloped, single-stranded positive-sense RNA viruses that belong to the Caliciviridae family along with norovirus
o Diagnosis: real-time PCR or multiplex PCR testing of a stool sample
How should this patient be managed?o No effective treatment for sapovirus infections
o Supportive treatment with intravenous fluids, antimotility agents (loperamide), and reduction of immunosuppression
o Tacrolimus levels should be closely monitored, as enterocyte damage can disrupt the P-glycoprotein efflux pump, leading to increased serum tacrolimus levels
o Nitazoxanide (limited evidence)
o Immunosuppressions: reducing MMF, switching mycophenolic acid to an enteric-coated mycophenolate or azathioprine
1-What is the differential diagnosis of diarrhoea following solid organ transplantation? Infectious
Ø Bacteria :Clostridium difficile , Campylobacter , Salmonella , Bacterial overgrowth, Aeromonas , Escherichia coli
Ø Viruses: CMV ,Norovirus ,Sapovirus , Rotavirus ,Adenovirus , Enterovirus
Ø Parasitic: Giardia , Cryptosporidium ,Isospora, Cyclospora, Microsporidium ,Entamoeba Noninfectious Immunosuppressives as Mycophenolate , Tacrolimus , Cyclosporine , Sirolimus Nonimmunosuppressive drugs as Antibacterial , Antiarrhythmic , Antidiabetic , Laxatives ,Proton pump inhibitors , Protease inhibitors Other
GVHD ,PTLD ,IBD , Colon cancer , Malabsorption 2-What should be included in the diagnostic evaluation of posttransplant diarrhoea?
Guidelines include discontinuation of any non immunosuppressive medications as PPI or oral hypoglycemics .
Microbial evaluation by C difficile PCR, CMV PCR, and multiplex PCR if available ,if all are negative , second-tier microbiological testing should include stool PCR for viral pathogen, ova, and parasite evaluation; giardia and cryptosporidium enzyme immunoassay; and breath test for bacterial overgrowth.
-If there was fever with diarrhea or pathogenic bacteria or parasite detected for antibacterial therapy.
– If no pathogen detected or Norovirus or Sapovirus then for supportive hydration and antimotility if diarrhea persists then for immunosuppression adjustment, if turned into persistening chronic diarrhea so for breath test to exclude small intestinal overgrowth treated with antibacterial therapy if non conclusive then for upper and lower endoscopy with biopsy
-CMV viremia for ganciclovir or valganciclovir then for upper and lower endoscopy with biopsy if needed
-Malabsorption as PTLD ,IBD,bloody diarrhea, CMV D+/R- then for upper and lower endoscopy with biopsy 3-What is the most likely explanation for this patient’s diarrhoea?
-Sapovirus infection leading to acute deterioration of chronic diarrhea and it came positive in stool PCR test
– AKI
4-How should this patient be managed?
-Volume repletion either oraly if tolerating or intravenous in severe dehydration,
-antimotility agents such as loperamide after excluding infectious cause .
-reduction of immunosuppression by decreasing Mycophenolate dose from 720 mg BID to 360 mg BID or switching to enteric-coated mycophenolate or azathioprine, having lower risk of developing posttransplant diarrhea
– as well as monitoring tacrolimus levels closely.
What is the differential diagnosis of diarrhoea following solid organ transplantation? Infectious
•Bacteria; Clostridium difficile,Campylobacter spp, Salmonella spp, Bacterial overgrowth, Aeromonas spp and Escherichia coli
•Viruses: CMV, Norovirus, Sapovirus, Rotavirus, Adenovirus, Enterovirus
• Parasitic; Giardia, Cryptosporidium, Isospora, Cyclospora, Microsporidium, Entamoeba
Noninfectious
•Immunosuppressive medications; MMF, Tacrolimus, Cyclosporine, Sirolimus
•Non-immunosuppressive medications; Antibacterial, Antiarrhythmic, Antidiabetic, Laxatives, PPI and Protease inhibitors
•Other: GVHD, PTLD, IBD, Colon cancer and Malabsorption What should be included in the diagnostic evaluation of posttransplant diarrhoea?
– First, to stop any non-immunosuppressive medications that may cause diarrhea.
– First line microbiological testing including: C. difficile PCR, CMV PCR, and multiplex PCR if available
– If previous first line tests were negative send for: stool PCR for viral pathogen, ova, and parasite evaluation; giardia and cryptosporidium enzyme immunoassay; and breath test for bacterial overgrowth.
– Additional consideration: EGD and colonoscopy with biopsy. What is the most likely explanation for this patient’s diarrhoea?
Fecal multiplex PCR was positive for sapovirus. The most likely diagnosis is sapovirus infection resulting in acute worsening of chronic diarrhea and AKI. How should this patient be managed? – No effective therapy against sapovirus infection.
– Symptomatic and supportive therapy: IV fluids, and antimotility agents; loperamide
– Reduction of IS ; reduce MMF from 720 BID to 360 BID, or switch MMF to EC-MPS or azathioprine.
– Monitor graft function closely while reducing IS
– Careful monitoring for tacrolimus level. – Nitazoxanid; antimicrobial agent evidence is limited to case report
IV fluid start specific to index patient how presented with severe diarrhea causing acute kidney injury. I appreciate that anti-motility start after excluding other possible infectious causes.
a) C.dificile. b) Campylobacter spp. c) Salmonella spp. e) bacterial overgrowth. f) Aeromonas spp. g) E.coli.
Viruses
a) CMV. b) Norovirus. c) Sapovirus. d) Rotavirus. e) Adenovirus. f) Enterovirus.
Parasitic
a) Giardia. b) Cryptosporidium. c) Isospora, Cyclospora. e) Microsporidium. f) Entameaba. 2. Non-infectious
Immunosuppressants
a) MMF. b) TAC. c) CyA. d) SIR.
Non-immunosuppressants medication
a) Antibacterial. b) Antiarrhythmic. c) Antidiabetic. e) Laxatives. f) PPIs. g) Protease inhibitors.
Others
a) GVHD. b) PTLD. c) IBD. d) Colon cancer. e) Malabsorption. Diagnostic evaluation
Stop all immunosuppressants medication that can cause diarrhea.
Microbial testing (C.dificile PCR, CMV PCR, and multiplex PCR) is the first line.
Second line if -ve 1st line (stool PCR for the viral pathogen, ova, and parasitic evaluation), (giardia and cryptosporidium enzyme immunoassay), (breath test for bacterial overgrowth).
The most likely cause of diarrhea in this patient
Saprovirus infection based on positive stool PCR.
Management of the Saprovirus infection
No proof till now of antiviral therapy for saprovirus infection.
Supportive treatment by IV fluid.
Antimotility agents (loperamide).
IS reduction to promote the immune system, (MMF dose reduced from 720 mg BD to 360 mg BD), or switch to enteric-coated mycophenolate or AZA, closely monitor kidney function to avoid rejection.
Close monitoring of the TAC level, as enterocyte damage, can disrupt the P-glycoprotein efflux pump, leading to an increased TAC level.
Nitazoxanide (antimicrobial agent with antiviral properties.
What should be included in the diagnostic evaluation of posttransplant diarrhoea
stop possible offending agents like MMF or TAC
PCR test for CMV, Clostridium Defficile, and faeca Multiplex test
If the above investigation comes back negative, then we do the following:
Stool PCR for a viral pathogen, ova, and parasite evaluation;
Giardia and cryptosporidium enzyme immunoassay; and
Breath test for bacterial overgrowth
What is the most likely explanation for this patient’s diarrhoea?
It is acute on chronic diarrhoea in post-transplant patient precipitated by Sapovirus infection, and complicated by acute kidney injury
How should this patient be managed?
To date, there is no definitive treatment for Sapovirus infection
Oral rehydration therapy if the patient is not vomiting, but if vomiting and hemodynamically unstable intravenous fluid will be better.
Reduce the dose of EC-MMF to 360mg BID
Close kidney function test because of reduction in MMF
Antimotility can be given after ruling out infective cause
What should included in diagnosis evaluation of post transplant diarrhea?
IDCP/AST guidelines include following test in evaluation of post transplant diarrhea:
Discontinuation of any non immunosuppression drug that can cause diarrhea as PPI, H2 agonist & oral hypoglycemic drugs.
First line microbiological test: C. difficile PCR, CMV PCR, bacterial culture or PCR for bacteria & multiplex PCR if available.
Second line microbiological test: Stool PCR for virus, ova & parasitize evaluation e.g. giardiasis & cryptosporidium enzyme immunoassay & breath test for bacterial overgrowth (if first line test result were negative).
EGD & colonoscopy with biopsy if there is suspicion of PTLD, CMV D+/R-, bloody diarrhea or family history of IBD.
What is the most likely explanation of this patient diarrhea:
Tac level is within target level.
First line microbiological test result were negative.
Stool ova, parasite & stool culture were negative.
Faecal multiplex PCR was positive for saprovirus
So the most likely diagnosis is saprovirus infection which can cause acute worsening of chronic diarrhea.
Saprovirus belongs to norvovirus family & its prevalence among post transplant patients is unknown.
How should this patient managed:
No effective treatment of saprovirus infection
IV fluid, anti-motility(lapromide) & reduction in immunosuppression can relief symptoms & clearance of virus.
Tac level should be monitored closely (enterocytic damage cause increase Tac level).
Nitazoxanide efficacy evidence is limited.
Reduce mycophenolate dose is common with some benefit regardless cause of diarrhea( but risk of rejection increased).
Switch mycophenolic acid to enteric coated mycophenolate or azathioprine associated with lower risk of post transplant diarrhea.
Why mention IV fluid to begin with in everyone with post transplant diarrhoea? Anti-motility (loperamide that your have spelt incorrectly) to be given only after ruling out infective causes.
Why not start with oral fluid replenishment unless a patient can not tolerate oral or the fluid deficit is too much to be replaced orally.
There are instances when we could not reinstate the patient to MMF and azathioprine was not possible due to that patient being on allopurinol, we have used sirolimus.
IV fluid start specific to index patient how presented with severe diarrhea causing acute kidney injury.
Anti-motility start after diagnosis of saprovirus infection & excluding other possible infectious causes.
Why mention IV fluid to begin with in everyone with post transplant diarrhoea? Anti-motility (loperamide) to be given only after ruling out infective causes.
Why not start with oral fluid replenishment unless a patient can not tolerate oral or the fluid deficit is too much to be replaced orally.
Yes, giving IV fluid or oral , it will depend on the patient clinical condition e.g hydration status, hemodynamics , the presence or absence of AKI, and the duration, frequency of the diarrhea. All these factors will decide the way to go. In these patient in particular IV is indicated due to worsening acute on chronic diarrhea and deterioration of his allograft function. So IV is justifiable here.
Yes, anti-motility after exclusion of infective causes. Although,sometimes these may not be an easy task
What is the differential diagnosis of diarrhea following solid organ transplantation?
Diarrhea is a frequent complication after transplantation, with 3-year posttransplant cumulative incidence reported to be around 22%. It has been associated with worse clinical outcomes, including acute kidney injury (AKI), supratherapeutic tacrolimus and mycophenolate levels, and decreased graft and patient survival.
The most common causes of diarrhea in patients after transplantation include infections, immunosuppressive medications, and antibiotics.
Noninfectious diarrhea in patients after transplantation
is commonly due to immunosuppressive drugs, with the highest incidence associated with mycophenolic acid.
Notably, patients with combined kidney-pancreas transplants are at a greater risk for rejectionand thushave higher exposure to immunosuppression compared to those with other solid organ transplants. Infectious diarrhea following kidney transplantation is frequently attributed to Clostridium difficile, CMV, and norovirus
What should be included in the diagnostic evaluation of diarrhea in patients after transplantation?
Current guidelines for evaluation of diarrhea in solid-organ transplant recipients from the Infectious Disease Community of Practice of the American Society of Transplantation start with stopping any nonimmunosuppressive medications that may cause diarrhea—such as proton pump inhibitors, H2
agonists,
and oral hypoglycemics—and first-line microbiological testing including Clostridium difficile polymerase chain reaction (PCR), CMV PCR, and multiplex PCR if available
What is the most likely explanation for this patient’s diarrhea?
Given the positive stool PCR, the most likely diagnosis is sapovirus infection resulting in acute worsening of chronic diarrhea. Several recent case reports have described sapovirus
infections leading to chronic, severe diarrhea in patients after kidney transplant.
How should this patient be managed?
Reducing mycophenolate dosage in response to posttransplant diarrhea is a common practice and has been shown to have some efficacy in patients with persistent diarrhea regardless of cause. However, caution should be used when opting for this treatment strategy, as reductions in mycophenolate dose have also been shown to be associated with rejection and decreased allograft survival.10 Other possible treatment options include switching mycophenolic acid to an enteric-coated mycophenolate or azathioprine, both of which have been associated with a lower risk of developing posttransplant diarrhea.
This patient was managed with intravenous fluids
and reduction of his mycophenolate dosage from 720 mg twice a day to 360 mg twice a day. By hospital day 3, his serum creatinine had returned to baseline with interval improvement of acute diarrhea. At 3 weeks follow-up, the patient showed marked clinical improvement, with 2 to 3 kg of weight gain and complete resolution of his acute-on-chronic diarrhea.
Diarrhoea in a Patient with Combined Kidney-Pancreas Transplant:
1. Differential diagnosis following solid organ transplantation
Infectious causes:
Non-infectious causes:
· Immunosuppressive medications such as mycophenolate, tacrolimus, cyclosporine, sirolimus, proton pump inhibitors, protease inhibitors
2. Diagnostic evaluation of post-transplant diarrhoea
Likely explanation for post-transplant diarrhoea
In the index case, the patient’s tacrolimus level was found to be within acceptable limits. First line microbiological testing was negative. Stool ova and parasite along with stool culture were also negative. However, fecal multiplex PCR was positive for sapo-virus, which could have been the reason for acute worsening of chronic diarrhoea in this patient.
Management of the patient
Sapovirus infection – a non-enveloped single stranded positive sense RNA virus.
Management includes
Ø Hydration Oral (intravenous, if poor oral intake or acutely ill)
Ø MPA dose reduction – allows immune system to clear infection
Ø Tacrolimus C0 levels monitoring – enterocyte damage can lead to increased serum tacrolimus levels
Ø Nitazoxanide – activates natural antiviral defence and inhibits cellular pathways that aid in viral replication
Ø If reduction in MPA dosage doesn’t help to clear viral infection but required further reduction, it cannot be done since this can damage the graft. In this case, consider switching to enteric coated mycophenolate, or azathioprine.
Ø Anti motility agents – loperamide, after treatment of pathogen.
Ø Follow up for patient’s appetite, weight gain, volume status, renal functions on frequent basis.
Differential diagnosis following solid organ transplantation
Diagnostic evaluation of post transplant diarrhoea
Likely explanation for post transplant diarrhoea
In the case discussed in the given article, the patient’s tacrolimus level was found to be within acceptable limits. First line microbiological testing was negative. Stool ova and parasite along with stool culture were also negative. However, on fecal multiplex PCR investigation, the patient was found to be positive for sapovirus. This should have been the reason for acute worsening of chronic diarrhoea that this patient had.
Management
This patient has sapovirus infection. Sapovirus is a non-enveloped single stranded positive sense RNA virus.
What is the differential diagnosis of diarrhoea following solid organ transplantation?
After transplantation, diarrhea is a common complication, with a 3-year cumulative incidence of diarrhea being reported to be approximately 22%.
Patients who have received a solid organ transplant are susceptible to infections, immunosuppressive drugs, and antibiotic-induced diarrhea.
Immunosuppressive medications frequently cause non-infectious diarrhea in transplant recipients, with mycophenolic acid having the greatest prevalence.
The common causes of infectious diarrhea after kidney donation include Clostridium difficile, CMV, and norovirus.
What should be included in the diagnostic evaluation of posttransplant diarrhoea?
Analyzing the root of diarrhea in a kidney transplant patient is crucial.
The first step in evaluating diarrhea in solid-organ transplant recipients according to current guidelines is to cease taking any non-immunosuppressive drugs that can make them sick.
If available, multiplex PCR, CMV PCR, and Clostridium difficile PCR are among the first-line microbiological tests.
Differential diagnosis for post renal Transplant Diarrhoea:
Infectious
•Bacterial (Clostridium difficile, Campylobacter spp., Salmonella spp., Bacterial overgrowth, Aeromonas spp., Escherichia coli)
•Viruses (CMV, Norovirus, Sapovirus, Rotavirus, Adenovirus, Enterovirus)
• Parasitic (Giardia, Cryptosporidium, Isosdpora, Cyclospora, Microsporidium, Entamoeba)
Noninfectious
•Immunosuppressive medications (Mycophenolate, Tacrolimus, Cyclosporine, Sirolimus)
•Nonimmunosuppressive medications as; Antibacterial, Antiarrhythmic, Antidiabetics, Laxatives, Proton pump inhibitors, Protease inhibitors)
•Other: GVHD, PTLD, IBD, Colon cancer, Malabsorption.
The diagnostic evaluation of post-transplant diarrhoea should include:
Stopping any non-immunosuppressive medications that may cause diarrhea as proton pump inhibitors, H2 agonists and oral hypoglycemics.
First-line microbiological testing including Clostridium difficile polymerase chain reaction (PCR), CMV PCR, and multiplex PCR if available.
Stool PCR for viral pathogen, ova, and parasite evaluation; giardia and cryptosporidium enzyme immunoassay; and breath test for bacterial overgrowth.
Colonoscopy and biopsy may be needed in some situations.
The most likely explanation for this patient’s diarrhoea
Is confirmed by positive stool PCR for Sapovirus infection resulting in acute worsening of chronic diarrhea.
Management should be:
Symptom relief with intravenous fluids for volume repletion and antimotility agents such as loperamide.
Reduction of immunosuppression especially the antimetabolite mycophenolate dosage.
Tacrolimus levels should be closely monitored.
Nitazoxanide can be tried as it is an antimicrobial agent with an antiviral effect by activating natural antiviral defenses and inhibiting cellular replication pathways.
Follow up for the patient’s appetite, weight gain, volume status, renal functions on frequent basis.
What is the differential diagnosis of diarrhoea following solid organ transplantation?The differential diagnosis of diarrhea following solid organ transplantation includes various infectious and noninfectious causes:
Infectious causes:
Noninfectious causes:
What should be included in the diagnostic evaluation of posttransplant diarrhoea?The diagnostic evaluation of posttransplant diarrhea in solid-organ transplant recipients should include the following steps:
What is the most likely explanation for this patient’s diarrhoea?In the given case, the most likely explanation for the patient’s diarrhea is sapovirus infection, which resulted in acute worsening of chronic diarrhea. This conclusion is based on the positive stool PCR for sapovirus.
How should this patient be managed?
What is the differential diagnosis of diarrhoea following solid organ transplantation?
What should be included in the diagnostic evaluation of posttransplant diarrhoea?
What is the most likely explanation for this patient’s diarrhoea? Since the patients clinical history and investigations are not supportive of any evidence of infection with a bakground of prolonged hiustory, it is likely non-infectious diarrhoea due to MMF
How should this patient be managed?
Differential diagnosis of post transplant diarrhea:
Infection:
Non infectious:
What should include in diagnosis evaluation of post-transplant diarrhoea?
What is the most likely explanation of this patient diarrhoea:
How should this patient have managed?
Diarrhoea in a Patient with Combined Kidney-Pancreas Transplant
DDX
Infection;
Non infectious;
Inclusion in diagnostic tests;
Most likely Dx;
Pt management;
■ What is the differential diagnosis of diarrhoea following solid organ transplantation?
◇ Infection agents :
● Bacteria
* Clostridium difficilea
* A Campylobacter spp.
* Salmonella spp.
* Bacterial overgrowtha
* Aeromonous spp.
* Escherichia coli
● Viruses
* CMV
* Norovirus
* Sapobavirus
* Rotavirus
* Adenovirus
● Parasitic
* Giardia
* Cryptosporidium
* Isosopora Cyclospora
* Microsporidium
* Entameoba
◇ Non Infection :
● Immunosurpressive medications
* MMF
* Tacrolimus
* Cyclosporine
* Sirolimus
● Nonimmunosuppressive medications
* Antibacterial
* Antiarrhythmic
* Antidiabetic
* Laxatives
* Proton pump inhibitors
* Protease inhibitors
● Other
* GVHDb
* PTLDb
* IBD
* Colon cancer
* Malabsorption
* Microscopic colitis
* Malakoplakia
■ What should be included in the diagnostic evaluation of posttransplant diarrhoea?
☆ Microbiological testing including Clostridium difficile PCR , CMV PCR, and multiplex PCR if available
☆ Stool PCR for viral pathogen, ova, and parasite evaluation; giardia and cryptosporidium enzyme immunoassay
☆ Breath test for bacterial overgrowth.
☆ Biopsy
☆ CMV IgM and or elevation in IgG
☆ Conventional culture
☆ Shell Vial assay
☆ CMV pp65 Ag
■ What is the most likely explanation for this patient’s diarrhoea?
Infections diarrhea with Sapobavirus that persist by immunosuppression drugs especially MMF
■ How should this patient be managed?
☆ Intravenous fluids
☆ Antimotility agents such as loperamide,
☆ Reduction of immunosuppression
☆ Monitore tacrolimus levels closely
☆ Antimicrobial agent as Nitazoxanide which activating natural antiviral defenses and inhibiting cellular pathways leading to viral replication
What is the differential diagnosis of diarrhea following solid organ transplantation?
Infectious
1-Bacteria: Clostridium difficile, Campylobacter spp, Salmonella spp, Bacterial overgrowth, Aeromonas spp, Escherichia coli
2-Viruses : CMV , Norovirus, Sapovirus , Rotavirus, Adenovirus , Enterovirus
3-Parasitic : Giardia, Cryptosporidium , Isospora, Cyclospora , Microsporidium ,Entamoeba
Noninfectious
1- Immunosuppressive medications Mycophenolate Tacrolimus, Cyclosporine, Sirolimus
2- Nonimmunosuppressive medications: Antibacterial, Antiarrhythmic, Antidiabetic, Laxatives, Proton pump inhibitors, Protease inhibitors
3- Other: GVHD , PTLD , IBD , Colon cancer, Malabsorption
2- What should be included in the diagnostic evaluation of posttransplant diarrhea?
first-line microbiological testing including Clostridium difficile polymerase chain reaction (PCR), CMV PCR, and multiplex PCR if available .If these tests return negative results, second-tier microbiological testing should include stool PCR for viral pathogen, ova, and parasite evaluation; giardia and cryptosporidium enzyme immunoassay; and breath test for bacterial overgrowth.
3- What is the most likely explanation for this patient’s diarrhea?
Given the positive stool PCR, the most likely diagnosis is sapovirus infection resulting in acute worsening of chronic diarrhea.
4-How should this patient be managed?
1) Good hydration with IV fluid.
2) Antimotility agents such as loperamide.
3) Reduction of immunosuppression to promote the immune system to clear the viral infection.
4) Nitazoxanide which is an antimicrobial agent that exerts its effect on viruses.
5) Close monitoring of tacrolimus.
What is the differential diagnosis of diarrhoea following solid organ transplantation?
Non infections:
INFECTIONS
2. What should be included in the diagnostic evaluation of posttransplant diarrhoea?
1- Clinical assessment to role out infection and new drugs
2- Start with stopping any non-immunosuppressive medications that may contribute like PPI, H2 blockers, and oral hypoglycemics
3- first-line microbiological testing including PCR for C Diff, CMV, and multiplex
4- Second microbiological testing: stool PCR for viral pathogen, ova, and parasite evaluation; giardia and cryptosporidium enzyme immunoassay; and breath test for bacterial overgrowth.
3. What is the most likely explanation for this patient’s diarrhoea?
sapovirus infection resulting in acute worsening of chronic diarrhea
4. How should this patient be managed?
This patient was managed with intravenous fluids and reduction of MMF
III. Diarrhoea in a Patient with Combined Kidney-Pancreas Transplant
What is the differential diagnosis of diarrhoea following solid organ transplantation?
Infectious
Bacterial
Clostridium difficile, Campylobacter spp., Salmonella spp., Bacterial overgrowth, Aeromonas spp., and Escherichia coli.
Viruses
CMV, Norovirus, Sapovirus, Rotavirus, Adenovirus, and Enterovirus.
Parasitic
Giardia, Cryptosporidium, Isosdpora, Cyclospora, Microsporidium, Entamoeba.
Noninfectious
Immunosuppressive medications
Mycophenolate, Tacrolimus, Cyclosporine and Sirolimus
Nonimmunosuppressive medications as
Antibacterial, Antiarrhythmic, Antidiabetics, Laxatives, Proton pump inhibitors, Protease inhibitors)
Other:
GVHD, PTLD, IBD, Colon cancer, Malabsorption.
What should be included in the diagnostic evaluation of posttransplant diarrhoea?
First we need to stop any non immunosuppressive medications that may cause diarrhea—such as proton pump inhibitors, H2 agonists, and oral hypoglycemic.
First-line microbiological testing including Clostridium difficile polymerase chain reaction (PCR),
CMV PCR, and multiplex PCR if available.
If above test negative second testing should include stool PCR for viral pathogen, ova, and parasite evaluation; giardia and cryptosporidium enzyme immunoassay; and breath test for bacterial overgrowth.
In this patient, tacrolimus level was found to be within desired therapeutic limits (7 ng/mL) and first line microbiological testing was negative.
Stool ova and parasite and stool culture were also negative.
Fecal multiplex PCR was positive for sapovirus
What is the most likely explanation for this patient’s diarrhoea?
Sapovirus infection.
How should this patient be managed
Intravenous fluid
Antimotility agent- loperamide
Reduction of immunosuppression
Close monitoring of the tacrolimus level
Limited data on Nitazoxanide
Differential diagnosis for post renal Transplant Diarrhoea:
Infectious
•Bacterial (Clostridium difficile, Campylobacter spp., Salmonella spp., Bacterial overgrowth, Aeromonas spp., Escherichia coli)
•Viruses (CMV, Norovirus, Sapovirus, Rotavirus, Adenovirus, Enterovirus)
• Parasitic (Giardia, Cryptosporidium, Isosdpora, Cyclospora, Microsporidium, Entamoeba)
Noninfectious
•Immunosuppressive medications (Mycophenolate, Tacrolimus, Cyclosporine, Sirolimus)
•Nonimmunosuppressive medications as; Antibacterial, Antiarrhythmic, Antidiabetics, Laxatives, Proton pump inhibitors, Protease inhibitors)
•Other: GVHD, PTLD, IBD, Colon cancer, Malabsorption.
The diagnostic evaluation of post-transplant diarrhoea should include:
Stopping any non-immunosuppressive medications that may cause diarrhea as proton pump inhibitors, H2 agonists and oral hypoglycemics.
First-line microbiological testing including Clostridium difficile polymerase chain reaction (PCR), CMV PCR, and multiplex PCR if available.
Stool PCR for viral pathogen, ova, and parasite evaluation; giardia and cryptosporidium enzyme immunoassay; and breath test for bacterial overgrowth.
Colonoscopy and biopsy may be needed in some situations.
The most likely explanation for this patient’s diarrhoea
Is confirmed by positive stool PCR for Sapovirus infection resulting in acute worsening of chronic diarrhea.
Management should be:
Symptom relief with intravenous fluids for volume repletion and antimotility agents such as loperamide.
Reduction of immunosuppression especially the antimetabolite mycophenolate dosage.
Tacrolimus levels should be closely monitored.
Nitazoxanide can be tried as it is an antimicrobial agent with an antiviral effect by activating natural antiviral defenses and inhibiting cellular replication pathways.
Follow up for the patient’s appetite, weight gain, volume status, renal functions on frequent basis.
III. Diarrhoea in a Patient with Combined Kidney-Pancreas Transplant
What is the differential diagnosis of diarrhoea following solid organ transplantation?
– Infectious:
– Noninfectious:
What should be included in the diagnostic evaluation of posttransplant diarrhoea?
– stop any non-immunosuppressive drugs that may cause diarrhoea e.g., PPIs, oral hypoglycemic agents, H₂ agonists
– 1st line microbiological tests i.e., serum/ blood CMV PCR/ NAT, stool C. difficile PCR, stool multiplex PCR, stool bacterial culture or PCR for bacterial pathogen
– if negative, proceed to 2nd tier microbiological tests i.e., evaluate for stool ova and parasites, stool viral PCR, stool giardia and cryptosporidium enzyme immunoassay (EIA), breath test for bacterial overgrowth
– if all the above are still negative, suspect other etiologies like malabsorption, PTLD, IBD consider doing OGD and colonoscopy with biopsy
What is the most likely explanation for this patient’s diarrhoea?
– sapovirus infection (detected in the fecal multiplex PCR ) causing an acute worsening of chronic diarrhoea
– this resulted in AKI due to volume depletion
– sapovirus infection has been associated with chronic, severe diarrhoea in kidney transplant recipients
How should this patient be managed?
– Tacrolimus trough level 7ng/mL
– 1st tier microbiological tests were negative (serum/ blood CMV PCR, stool C. difficile PCR, stool bacterial culture or stool bacterial PCR), stool ova and parasite, stool culture were also negative but fecal multiplex PCR was positive for sapovirus
– currently there are no therapies that have been shown to be effective in treating sapovirus infections
– hydration (IVF), antimotility drugs (e.g., loperamide), reduction in immunosuppression to promote the immune system to clear the viral infection
– enterocyte damage can disrupt the P-glycoprotein efflux pump leading to increased tacrolimus levels, hence monitor tacrolimus trough levels closely
– nitazoxanide has also been used with limited evidence (case reports), it is an antimicrobial agent which activates the natural antiviral defenses and inhibits the cellular pathways which lead to viral replication
– reduction in mycophenolate is a common practice, it has some efficacy in patients with persistent diarrhoea regardless of the cause
– caution should be observed since reduction in MPA dose may result in rejection and decreased graft survival
– the other option is switching from MMF to enteric coated mycophenolate or azathioprine since both of them are associated with a lower risk of developing posttransplant diarrhoea
– management of our case: IV hydration, reduction in immunosuppression (mycophenolate 720mg BD to 360mg BD)
– by day 3, the serum creatinine had normalized, the diarrhoea had subsided
– during his follow up, by week 3, there was significant clinical improvement, there was a complete resolution of the diarrhoea, with a 2-3kg weight gain
1. What is the differential diagnosis of diarrhoea following solid organ transplantation?
· Diarrhea is a frequent complication after transplantation, with 3-year posttransplant cumulative incidence reported to be around 22%.
· The most common causes of diarrhea in patients after transplantation include infections, immunosuppressive medications, and antibiotics.
· Noninfectious diarrhea in patients after transplantation is commonly due to immunosuppressive drugs, with the highest incidence associated with mycophenolic acid.Notably, patients with combined kidney-pancreas transplants are at a greater risk for rejection and thus have higher exposure to immunosuppression compared to those with other solid organ transplants.
· Infectious diarrhea following kidney transplantation is frequently attributed to Clostridium difficile, CMV, and norovirus.
2. What should be included in the diagnostic evaluation of posttransplant diarrhoea?
· start with stopping any nonimmunosuppressive medications that may cause diarrhea—such as proton pump inhibitors, H2 agonists, and oral hypoglycemics—and first-line microbiological testing including Clostridium difficile polymerase chain reaction (PCR), CMV PCR, and multiplex PCR if available.
· If these tests return negative results, second-tier microbiological testing should include stool PCR for viral pathogen, ova, and parasite evaluation; giardia and cryptosporidium enzyme immunoassay; and breath test for bacterial overgrowth.
· In this patient, tacrolimus level was found to be within desired therapeutic limits (7 ng/mL) and first[1]line microbiological testing was negative.
· Stool ova and parasite and stool culture were also negative.
· Fecal multiplex PCR was positive for sapovirus
3. What is the most likely explanation for this patient’s diarrhoea?
· Given the positive stool PCR, the most likely diagnosis is sapovirus infection resulting in acute worsening of chronic diarrhea.
· Several recent case reports have described sapovirus infections leading to chronic, severe diarrhea in patients after kidney transplant. The prevalence of posttransplant sapovirus is unknown.
· Diagnosis is typically made via real-time PCR or multiplex PCR testing of a stool sample.
4. How should this patient be managed?
· To date there have been no therapies shown to be effective in treating sapovirus infections.
· Previous reports have demonstrated symptom relief with intravenous fluids,antimotility agents such as loperamide, and reduction of immunosuppression to promote the immune system to clear the viral infection.
· In addition,tacrolimus levels should be closely monitored, as enterocyte damage can disrupt the P-glycoprotein efflux pump, leading to increased serum tacrolimus levels.
· Limited case studies have also suggested nitazoxanide as a potential therapeutic agent.
· Nitazoxanide is an antimicrobial agent that exerts its effect on viruses by activating natural antiviral defenses and inhibiting cellular pathways leading to viral replication. but Currently, evidence for its efficacy is limited to case reports.
· This patient was managed with intravenous fluids and reduction of his mycophenolate dosage from 720 mg twice a day to 360 mg twice a day.
· By hospital day 3, his serum creatinine had returned to baseline with interval improvement of acute diarrhea.
· At 3 weeks follow-up, the patient showed marked clinical improvement, with 2 to 3 kg of weight gain and complete resolution of his acute-on-chronic diarrhea.
· Reducing mycophenolate dosage in response to post[1]transplant diarrhea is a common practice and has been shown to have some efficacy in patients with persistent diarrhea regardless of cause.
· However, caution should be used when opting for this treatment strategy, as reductions in mycophenolate dose have also been shown to be associated with rejection and decreased allograft survival. Other possible treatment options include switching mycophenolic acid to an enteric-coated mycophenolate or azathioprine, both of which have been associated with a lower risk of developing posttransplant diarrhea.
What is the differential diagnosis of diarrhoea following solid organ transplantation?This can be divided into:
1) Non-infectious cause
2) Infectious cause
What should be included in the diagnostic evaluation of posttransplant diarrhoea?
What is the most likely explanation for this patient’s diarrhoea?
How should this patient be managed?
Diarrhea in a Patient With Combined Kidney- Pancreas Transplant
Q1- What is the differential diagnosis of diarrhoea following solid organ transplantation?
Causes:
Simply classified in to two group :
either infectious or none infectious .
1- Infectious etiology : ( common cause are CMV and Clostridium difficile)
Viral: CMV (most common), Norovirus, Rotavirus, Adenovirus, Sapobavirus
Bacterial: Clostridium difficile, Campylobacter, Salmonella, E coli, Bacterial overgrowth.
Parasitic: Cryptosporidium, Giardia, Isosopora Cyclospora, Microsporidium and Entameoba.
2- None infectious etiology :
a- Drug induced:
Immunosuppressive drugs (MMF mainly, CNI and MTORi).
Others (laxatives, anti-diabetics, PPI, antiarrhythmic drugs).
b- Other disorders:
GVHD, IBD, PTLD, cancer colon, malabsorption and microscopic colitis .
Causes of posttransplant diarrhea
Infection Noninfection
Bacteria Immunosurpressive medications
Clostridium difficilea MMFa
Campylobacter spp. Tacrolimus
Salmonella spp. Cyclosporine
Bacterial overgrowtha Sirolimus
Aeromonous spp.
Escherichia coli
Viruses Nonimmunosuppressive medications
CMVa Antibacterial
Norovirus Antiarrhythmic
Sapobavirus Antidiabetic
Rotavirus Laxatives
Adenovirus Proton pump inhibitors
Protease inhibitors
Parasitic Other
Giardia GVHD
Cryptosporidium PTLD
Isosopora Cyclospora IBD
Microsporidium Colon cancer
Entameoba Malabsorption
Microscopic colitis
Malakoplakia
Q2- What should be included in the diagnostic evaluation of posttransplant diarrhoea?
History : should include
onset,
durations
associated symptoms ( fever, weight loss, relationship to meals, any blood in the stool, upper GIT manifestations and family history of same condition )
determine the offending drug and if it possible stop it : PPI , H2 agonists, Oral hypoglycemic agents .
Examination: for sign of dehydration, signs of infection , or lymphadenopathy, hepatosplenomegaly, skin rash.
Investigations :
GSE , stool for c/s . , CMV PCR.
Stool for C.difficile antigen & PCR , Clostridium difficile (PCR).
Stool for biofire for both bacteria and viruses .
Blood cultures and sensitivity.
Modified ZN stain for cryptosporidium.
Invasive – Colonoscopy
Breath test for bacterial overgrowth
Q3 What is the most likely explanation for this patient’s diarrhoea?
Most likely explanation is :
· presentation – chronic diarrhea and significant weight loss .
· positive for sapovirus by PCR may suggest the cause ·
. invasive CMV .
Q4 How should this patient be managed?
– No specific effective drug for sapovirus infections , but some studies suggested nitazoxanide as a potential therapeutic option.
– Supportive therapy: IV fluids , antimotility , and manipulation of immunosuppression- step wise reduction ·
– The index case is treated by intravenous fluids and reduction of immunosuppressive drug , with good response .
What is the differential diagnosis of diarrhea following solid organ transplantation?
Diarrhea post kidney transplant is common complications and has many causes such as infectious and non-infectious which is mainly related to immunosuppression medications or other drugs induced diarrhea.
D.D:
Infectious causes such as :bacterial, viral, and parasitic causes.
Non-infectious causes such as : Immunosuppressive medications, non-immunosuppressive medications and others (GVHD, PTLD, IBD, Colon cancer, and Malabsorption) ,
What should be included in the diagnostic evaluation of posttransplant diarrhea?
Microbiological testing including Clostridium difficile polymerase chain reaction
(PCR), CMV PCR, and multiplex PCR if available .
Stool PCR for viral pathogen, ova, and parasite evaluation; giardia and cryptosporidium enzyme immunoassay; and breath test for bacterial overgrowth
• What is the most likely explanation for this patient’s diarrhea?
Infectious cause of diarrhea as multiplex PCR was positive for sapovirus which led to worsening of chronic diarrhea.
• How should this patient be managed?
1-Intravenous fluids for adequate hydration.
2-Antimotility agents such as loperamide.
3-Reduction of immunosuppression to promote the immune system to clear the viral infection.
4-Nitazoxanide is an antimicrobial agent that exerts its effect on viruses.
5-Close monitoring of tacrolimus.
What is the differential diagnosis of diarrhoea following solid organ transplantation.
Infectious
•Bacteria :Clostridium difficile, Campylobacter spp, Salmonella spp, Bacterial overgrowth, Aeromonas spp, Escherichia coli
•Viruses : CMV , Norovirus, Sapovirus , Rotavirus, Adenovirus , Enterovirus
•Parasitic : Giardia, Cryptosporidium , Isospora, Cyclospora , Microsporidium ,Entamoeba
Noninfectious
•Immunosuppressive medications : Mycophenolate ,Tacrolimus, Cyclosporine, Sirolimus
•Nonimmunosuppressive medications : Antibacterial, Antiarrhythmic, Antidiabetic, Laxatives, Proton pump inhibitors, Protease inhibitors •Other: GVHD , PTLD , IBD , Colon cancer, Malabsorption
What should be included in the diagnostic evaluation of posttransplant diarrhoea?
1.Stopping any nonimmunosuppressive medications that may cause diarrhea.
such as proton pump inhibitors, H2 agonists, and oral hypoglycemic.
2-First-line microbiological testing;
Including; Clostridium difficile polymerase chain reaction (PCR), CMV PCR, and multiplex PCR
-If these tests return negative results,
3-Second-line microbiological testing;
Including; stool PCR for viral pathogen, ova, and parasite evaluation; giardia and cryptosporidium enzyme immunoassay; and breath test for bacterial overgrowth. Than EGD, Colonoscopy with biopsy.
What is the most likely explanation for this patient’s diarrhoea?
Fecal multiplex PCR was positive for sapovirus infection causing acute worsening of chronic diarrhea.
How should this patient be managed?
There is no definitive therapies shown to be effective in treating sapovirus infections.
–Oral hydration if not tolerated iv hydration
–Reduce the dose of EC-MMF to 360mg BID.
–Monitor of Tacrolimus level.
–Kidney function test monitoring because of reduction in MMF.
–Antimotility agents such as loperamide can be given once infection is excluded.
–Limited case studies have also suggested Nitazoxanide as a potential therapeutic agent.
differential diagnosis of diarrhoea following solid organ transplantation
1- Infectious
•Bacteria Clostridium difficile , Campylobacter spp. , Salmonella spp. , Bacterial overgrowth , Aeromonas spp., Escherichia coli
•Viruses CMV, Norovirus, Sapovirus, Rotavirus, Adenovirus, Enterovirus
•Parasitic Giardia, Cryptosporidium, Isospora, Cyclospora, Microsporidium, Entamoeba
2- Noninfectious
•Immunosuppressive medications Mycophenolate, Tacrolimus, Cyclosporine, Sirolimus
•Nonimmunosuppressive medications Antibacterial, Antiarrhythmic, Antidiabetic, Laxatives, Proton pump inhibitors, Protease inhibitors
3- Other GVHD, PTLD, IBD, Colon cancer, Malabsorption
What should be included in the diagnostic evaluation of posttransplant diarrhoea1- stop non immunosuppressive medications if diarrhea persist:
2- do test on stool examination for clostridium difficile and bacterial overgrowth if diarrhea persist and test are negative
3-multiplex PCR of stool sample on various pathogens
3- do CMV PCR if negative
4-manipulate immunosuppressive medications guided by trough levels and TDM
What is the most likely explanation for this patient’s diarrhoea
Sapoviruses recent infection?? confirmed by PCR multiplex on stool sample
How should this patient be managed1- hospitalization and supportive treatment iv fluids
2- decrease dose of myfortic
3-antimotility and antimicrobial drugs
1-What is the differential diagnosis of diarrhoea following solid organ transplantation.
Infectious :
Bacteria ;
Clostridium difficile Campylobacter spp. Salmonella spp.
Bacterial overgrowth Aeromonas spp. Escherichia coli
Viruses ;
CMV Norovirus Sapovirus
Rotavirus Adenovirus Enterovirus
Parasitic ;
Giardia Cryptosporidium Isospora , Cyclospora Microsporidium Entamoeba
Noninfectious :
Immunosuppressive medications ;
Mycophenolate Tacrolimus Cyclosporine Sirolimus
Nonimmunosuppressive medications;
Antibacterial Antiarrhythmic Antidiabetic Laxatives
Proton pump inhibitors Protease inhibitors
Others ;
GVHD PTLD IBD Colon cancer Malabsorption
2-What should be included in the diagnostic evaluation of posttransplant diarrhoea?
1-Stopping any nonimmunosuppressive medications that may cause diarrhea;
such as proton pump inhibitors, H2 agonists, and oral hypoglycemic.
2-First-line microbiological testing;
Including; Clostridium difficile polymerase chain reaction (PCR), CMV PCR, and multiplex PCR if available.
-If these tests return negative results,
3-Second-line microbiological testing;
Including; stool PCR for viral pathogen, ova, and parasite evaluation; giardia and cryptosporidium enzyme immunoassay; and breath test for bacterial overgrowth.
3-What is the most likely explanation for this patient’s diarrhoea?
-Fecal multiplex PCR was positive for sapovirus;(nonenveloped, single-stranded positive-sense RNA viruses that belong to the Caliciviridae family along with norovirus).
-The most likely diagnosis is sapovirus infection resulting in acute worsening of chronic diarrhea.
4-How should this patient be managed?
–To date, there is no therapies shown to be effective in treating sapovirus infections.
–As pt is hemodynamically stable and no vomiting to encourage him for good oral hydration, but if has vomiting and hemodynamically unstable intravenous fluid should be started.
–Reduce the dose of EC-MMF to 360mg BID.
–Close monitoring of Tacrolimus level.
–Close kidney function test because of reduction in MMF.
–Antimotility agents such as loperamide can be given after R/O infective causes.
–Limited case studies have also suggested Nitazoxanide as a potential therapeutic agent.
Diarrhoea in a Patient with Combined Kidney-Pancreas Transplant
1. What is the differential diagnosis of diarrhoea following solid organ transplantation?
2. What should be included in the diagnostic evaluation of posttransplant diarrhoea?
3. What is the most likely explanation for this patient’s diarrhoea?
4. How should this patient be managed?
The differential diagnosis of diarrhea following solid organ transplantation includes:
Diarrhea is one of the most common complaints in post-transplant. Almost 25% of recipients develop diarrhea which disturbs their quality of life.
Infectious Causes:
Bacterial:
Clostridium difficile
E. coli
Campylobacter jejunii
Salmonella species
Bacterial overgrowth syndrome
Aeromonas species
Tuberculous colitis
Viral:
CMV
Norovirus
Sapovirus
Rotavirus
Adenovirus
Enterovirus
Parasites:
Giardia lamblia
Cryptosporidium parvum
Microsporidioisis
Isosporal belli
Entameba histolytic
Non-Infectious
Drugs:
Immunosuppressants:
Mycophenolate mofetil
CNIs: Tacrolimus & Cyclosporine
Sirolimus
Non-immunosuppressants:
Antimicrobials
Proton pump inhibitors
H2 receptor antagonists
Laxatives
ARVs – protease inhibitors
Antiarrhythmics
Other Causes:
Colon cancer
GVHD
Inflammatory bowel disease
Malabsorption syndromes
What should be included in the diagnostic evaluation of posttransplant diarrhoea?
Detailed history should be taken about onset, course and durations of diarrhea and if there are any symptoms of infection like fever, weight loss, relationship to meals, any blood in the stool, upper GIT manifestations and any other family member developed same picture.
We should discontinue the following drugs:
Proton pump inhibitors, H2 agonists, Oral hypoglycemic.
Examination: looking for any signs of infection or malignancy lymphadenopathy, hepatosplenomegaly
Laboratory investigations:
Stool microscopy and culture
The Common Tests to be done; Clostridium difficile polymerase chain reaction (PCR), CMV PCR.
Stool for C.difficile antigen and PCR
Stool for biofire for both bacteria and viruses
CMV PCR
Blood cultures
Modified ZN stain for cryptosporidium.
Colonoscopy – To assess for colitis.
Breath test for bacterial overgrowth
·
What is the most likely explanation for this patient’s diarrhoea?
The patient had a positive stool test for sapovirus – so that was the cause of the diarrhea, which can be diagnosed by real-time PCR or multiplex PCR testing of stool samples.
However, the patient is also on enteric coated mycophenolate sodium at 720 mg twice daily – although it is the enteric coated mycophenolate sodium and not the mycophenolate mofetil – it can also cause diarrhea and it is at a high dose three years post-transplant.
How should this patient be managed?
If your patients with symptoms and signs of Effective arterial blood volume depletion (JVP, Chest, LL edema, Orthostatic changes….) , History of previous AKI you should start managing with;
Intravenous fluids, UOP chart.
Reduction of immunosuppression to promote the immune system.
Reduce the dose of the EC-mycophenolate sodium to 360 mg BD while closely monitoring the graft function.
Other possible treatment options include switching of immunosuppressant. He is already on enteric-coated mycophenolate so I may need to shift to azathioprine, both of which have been associated with a lower risk of developing post-transplant diarrhea.
Not many patients benefit from conversion conversion of MMF to myfortic. Please change to azathioprine or to a smaller dose sirolimus as an adjunct if that patient cannot be giving azathioprine to avoid interaction with allopurinol.
Tacrolimus levels should also be monitored, as enterocyte damage can disrupt the P-glycoprotein efflux pump.
Monitor the tacrolimus levels and mycophendlate levels as enterocyte damage due to the chronic diarrhea can cause increased absorption and toxicity.
Nitazoxanide is an antimicrobial agent that exerts its effect on viruses by activating natural antiviral defenses and inhibiting cellular pathways leading to viral replication.
Antimotility agents such as loperamide after exclusion of infectious causes,
The differential diagnosis of diarrhea following solid organ transplantation includes:
Infectious Causes:
Bacterial:
Viral:
Parasites:
Non-Infectious
Drugs:
Immunosuppressants:
Non-immunosuppressants:
Antiarrhythmics
Other Causes:
Diagnostic Evaluation:
Likely explanation for the patients diarrhea:
Management:
Infectious causes :
Noninfectious causes :
Others:
GVHD , PTLD , IBD , Colon cancer , Malabsorption
What should be included in the diagnostic evaluation of posttransplant diarrhoea?
Stool analysis for ova, and parasite evaluation, giardia gram stain , Stool culture ,PCR for viral, cryptosporidium enzyme immunoassay, and breath test for bacterial overgrowth.
What is the most likely explanation for this patient’s diarrhoea?
The most likely cause of chronic diarrhea in patients after kidney transplant is sapovirus infection which can be diagnosed by real-time PCR or multiplex PCR testing of stool samples.
How should this patient be managed?
The patient should be assessed regarding symptoms and signs of dehydration but he is already having frequent motions with AKI so I will start managing
What is the differential diagnosis of diarrhea following solid organ transplantation?
– Infectious
o Bacteria
Clostridium difficile.
Campylobacter spp.
Salmonella spp.
Bacterial overgrowth.
Aeromonas spp.
Escherichia coli.
o Viruses
CMV.
Norovirus
Sapovirus
Rotavirus.
Adenovirus.
Enterovirus.
o Parasitic
Giardia
Cryptosporidium
Isospora, Cyclospora
Microsporidium.
Entamoeba
– Noninfectious
o Immunosuppressive medications.
Mycophenolate.
Tacrolimus.
Cyclosporine.
Sirolimus.
o Nonimmunosuppressive medications.
Antibacterial
Antiarrhythmic
Antidiabetic
Laxatives
Proton pump inhibitors
Protease inhibitors.
o Other
GVHD
PTLD
IBD
Colon cancer
Malabsorption
What should be included in the diagnostic evaluation of posttransplant diarrhea?
· It is critical to stop any nonimmunosuppressive medications that may cause diarrhea—such as
o Proton pump inhibitors,
o H2 agonists,
o Oral hypoglycemic
· First-line microbiological testing including
o Clostridium difficile polymerase chain reaction (PCR),
o CMV PCR,
o Multiplex PCR if available
· If these tests return negative results, second-tier microbiological testing should include:
o Stool PCR for the viral pathogen, ova, and parasite evaluation; giardia and cryptosporidium enzyme immunoassay;
o Breath test for bacterial overgrowth.
· EGD, Colonoscopy with biopsy.
What is the most likely explanation for this patient’s diarrhea?
Given the positive stool PCR, sapovirus infection, which causes sudden exacerbation of chronic diarrhea, is the most likely diagnosis.
How should this patient be managed?
There are currently no treatments that have been demonstrated to be successful in treating sapovirus infections.
Past studies have shown that:
• Intravenous fluids, antimotility medications such loperamide,
• Immunosuppression should be reduced to encourage the immune system to fight off the viral infection.
• It is important to closely monitor tacrolimus levels because enterocyte injury can impair the P-glycoprotein efflux pump, which raises the concentration of tacrolimus in the blood.
• Nitazoxanide has also been mentioned as a potential therapeutic drug in a few case reports.
• Patients with persistent diarrhea, regardless of the etiology, may benefit from reducing their mycophenolate dosage as a reaction to posttransplant diarrhea.
My caution: antimotility agents such as loperamide ONLY after excluding infectious cause .
Absolutely.
Thanks a lot, dear professor.
So nice of you Dr Saiwan
1.What is the differential diagnosis of diarrhoea following solid organ transplantation?Diarrhoea in the post transplant can be divided into infectious and non-infectious causes.
Non-infectious causes are mainly attributed to drugs and they include:
Infectious causes: Most infectious causes in the post-transplant is CMV.
• Other causes:
What should be included in the diagnostic evaluation of post-transplant diarrhoea?Current guidelines for evaluation of diarrhoea in solid-organ transplant recipients from the Infectious Disease Community of Practice of the American Society of Transplantation state:
First tier microbiological testing:
Second tier microbiological testing:
Colonoscopy with biopsy may be considered as a final step.
What is the most likely explanation for this patient’s diarrhoea?Sapovirus
How should this patient be managed?Reduction of immunosuppressive agents to allow the immune system to clear the virus.
Close monitoring of the tacrolimus trough levels, the enterocyte damage can disrupt p-glycoprotein efflux pump leading to increased tacrolimus levels.
Nitazoxide has potential therapeutic potential, though evidence of its use is limited to case reports.
Other treatment options: use of anti motility agents- loperamide, IVF rehydration.
Not many patients benefit from conversion conversion of MMF to myfortic.
Ø Differential diagnosis of diarrhea post transplantation:
· Infectious diarrhea (viral as CMV, norovirus, rotavirus, adenovirus), bacterial (Cl-difficile, salmonella, E coli, campylobacter), protozoa (cryptosporidium, giardia and microsporidia). While most common are CMV, cl-difficle and Norovirus.
· Drug induced (IS as MMF and CNI), others as PPI, laxatives and prolonged use of antimicrobial.
· Other disorders as duodenal villous atrophy, IBD like and GVHD.
Ø What should be included in diagnostic evaluation of diarrhea post transplantation:
· Step wise approach is used.
· Stop any non immunosuppressive drugs as PPI, H2 agonists and oral hypoglycemics.
· Then test for Clostridium difficile PCR, CMV PCR, and multiplex PCR if available.
· If above-mentioned tests are -ve, proceed to stool PCR for viral pathogen, ova, and parasite evaluation; giardia and cryptosporidium enzyme immunoassay; and breath test for bacterial overgrowth.
Ø Most likely explanation of index case:
· The index case is presented with chronic diarrhea and significant weight loss.
· Fecal multiplex PCR was positive for sapovirus which suggests that it is the cause of worsening diarrhea.
· Note that, he has high risk for CMV infection due serological status (D+/R-), plus over immunosuppression used in cases with combined kidney and pancreas transplantation (as they have very high risk of AR), but here CMV PCR ids negative (it can be -ve in 15 % of cases with CMV tissue invasive disease and diagnosis requires endoscopy and tissue biopsy).
Ø Treatment of the index case:
o No specific anti-viral therapy is available.
o Just supportive therapy with intravenous fluids, antimotility agents such as loperamide, and reduction of immunosuppression (especially MMF or shift to EC-MPS or AZA), but with caution and close monitoring of the graft function to guard against AR.
o Nitazoxanide is an antimicrobial with ? antiviral properties and inhibit cellular pathways required for viral replication.
Why mention IV fluids to begin with in everyone with post transplant diarrhoea?
My caution: antimotility agents such as loperamide ONLY after excluding infectious cause .
Not many patient benefit from conversion conversion of MMF to myfortic. Please change to azathioprine or to a smaller dose sirolimus as an adjunct if that patient can not be give azathioprine to avoid interaction with allopurinol.
1.What is the differential diagnosis of diarrhoea following solid organ transplantation?
Infections, IS drugs, & antibiotics are the most frequent causes of diarrhea post SOT.
IS medications frequently cause non-infectious diarrhea in SOT recipients, with mycophenolic acid having the highest prevalence.
Compared to recipients of other SOT, patients with combined kidney-pancreas TX are more likely to have immunosuppression due to a higher risk of rejection.
The common causes of infectious diarrhea after KTX are Clostridium difficile, CMV, & norovirus.
===========================
2.What should be included in the diagnostic evaluation of posttransplant diarrhea?
Determining the origin of diarrhea, since pinpointing the source can enable targeted treatment.
Stopping any non-immunosuppressive medications that may cause diarrhea—such as PPIs, H2 agonists, diuretics, & oral hypoglycemic
1st-line microbiological testing (CDI PCR, CMV PCR, & multiplex PCR, if available).
2nd-tier microbiological testing should consist of stool PCR for the viral pathogens, ova, & parasites, giardia & cryptosporidium enzyme immunoassay, and breath test for bacterial overgrowth if 1st tier tests yield negative results.
===========================
3.What is the most likely explanation for this patient’s diarrhoea?
Tacrolimus levels in this patient were within the targeted therapeutic range (7 ng/mL), & initial microbiological testing came out negative.
The stool culture, stool ova, & stool parasite tests were all negative.
Fecal multiplex PCR detected sapovirus. Hence, sapovirus infection causing an acute exacerbation of chronic diarrhea is the most likely diagnosis.
Along with norovirus, sapoviruses are members of the Caliciviridae family of ss RNA viruses.
One multiplex PCR assay checks for a range of stool pathogens, including viruses, bacteria, & parasites including Cryptosporidium, Cyclospora cayetanensis, Entamoeba histolytica, & Giardia lamblia.
===========================
4.How should this patient be managed?
No specific therapy for sapovirus.
Treatment is supportive with IV fluids, antimotility agents (loperamide), & reduction of IS medications to promote the immune system to clear the viral infection.
Regular monitor of tacrolimus levels because enterocyte damage can impair the P-glycoprotein efflux pump, which raises the tacrolimus blood levels.
Reduction of MMF dosage from 720 mg twice a day to 360 mg twice a day. Caution should be used as reductions
in MMF are associated with rejection & reduced graft survival.
Changing from MMF to an EC-MPS or AZA, both of which have been linked to a lower risk of developing diarrhea, are further therapeutic choices.
Why mention IV fluids to begin with in everyone with post transplant diarrhoea?
My caution: antimotility agents such as loperamide ONLY after excluding infectious cause .
What is the differential diagnosis of diarrhoea following solid organ transplantation?
Infectious:
•Bacteria B Clostridium difficile B Campylobacter spp. B Salmonella spp. B Bacterial overgrowth B Aeromonas spp. B Escherichia coli
•Viruses B CMV B Norovirus B Sapovirus B Rotavirus B Adenovirus B Enterovirus
•Parasitic B Giardia B Cryptosporidium B Isospora, Cyclospora B Microsporidium B Entamoeba Noninfectious.
Immunosuppressive medications:
Mycophenolate.
Tacrolimus.
Cyclosporine.
Sirolimus.
Nonimmunosuppressive medications:
Antibacterial, Antiarrhythmic, Antidiabetic, Laxatives. Proton pump inhibitors, and Protease inhibitors.
Others:
GVHD.
PTLD.
IBD.
Colon cancer.
Malabsorption.
What should be included in the diagnostic evaluation of posttransplant diarrhoea?
Current guidelines for evaluation of diarrhea in solid-organ transplant recipients from the Infectious Disease Community of Practice of the American Society of Transplantation:
(1) Stop non-immunosuppressive medications causing diarrhea, example PPI.
(2) Microbilogical tresting:
– Clostridium difficile polymerase chain reaction (PCR), CMV PCR, and multiplex PCR if available.
– microbiological testing should include stool PCR for viral pathogen, ova, and parasite evaluation; giardia and cryptosporidium enzyme immunoassay; and breath test for bacterial overgrowth.
(3) immunosuppressive manibulation – reducing the dose of MMF or shifting to EC-MPA ,or azathioprine.
What is the most likely explanation for this patient’s diarrhoea?
By exclusion of the most common causes of infectious diarrhea C.difficle, CMV, and bacterial stool cultures, multiplex PCR might be of benefit.
Positive stool PCR for sapovirus, causing acute on top of chronic diarrhea, with worsening kidney function.
Sapovirus infections is a single stranded positive sense RNA virus (Caliciviridae family), can lead to chronic, severe diarrhea in patients after kidney transplant, and diagnosis is made via real-time PCR or multiplex PCR testing.
How should this patient be managed?
IV hydration with isotonic solutions and correction of electrolytes derrangment.
Antimotalilty – loperamide.
Reduction of immunosupreesive medications, promoting immune system to eliminate the virus.
Reducing MMF dose by 50% (but might increase the risk of rejection), so switching to EC-MPA, or azathioprine may be beneficial and protect against rejection.
Close monitoring of tacrolimus level, to keep therapeutic level with close monitoring of graft function.
Nitazoxanide is an antimicrobial agent poses anti-viral activity by energizing cellular pathways that support viral replication and natural antiviral defenses, in case reports only.
Why mention IV fluids to begin with in everyone with post transplant diarrhoea?
My caution: antimotility agents such as loperamide ONLY after excluding infectious cause .
In transplant patients, diarrhea is frequent. While the majority of cases are minor and short-lived, some are serious and persistent, which puts graft at risk by causing dehydration, so preemptive iv crystalloid may be helpfull, with correction of electrolytes.
diarrhea cause normal anion gap acidosis which may be resposive to iv fluids and isotonic bicarbonate
Diarrhea in a Patient With Combined Kidney-
Pancreas Transplant
American Journal of Medicine.
Causes of post-transplant diarrhea
A- Infectious diarrhea
B-Non-infectious diarrhea
· Drug induced: MMF, CNI, sirolimus, antibiotics, proton pump inhibitors
· Malignancy such as cancer colon, PTLD
How to approach:
The main important issue is to differentiate between infectious causes from noninfectious causes
1- detailed history should be taken about onset, course and durations of diarrhea and if there is any symptoms of infection like fever, upper GIT manifestations and any other family member developed same picture.
2- Examination: looking for any signs of infection or malignancy
3- Investigations include:
· Primary investigations including CNI level, CMV PCR, Stool culture and CD toxin in stool
· Secondary investigations (if primary investigations were not conclusive) including stool multiplex PCR for viral, bacterial and parasitic infection (Cryptosporidium, Entamoeba histolytica, Giardia lamblia, Campylobacter, Shigella, Salmonella, Vibrio, Yersinia enterocolitica, adenovirus and sapovirus), enzyme immunoassay for giardia and cryptosporidium and breath test for bacterial overgrowth
· Imaging, colonoscopy, and biopsy may be needed if there is suspicious of malignancy or CMV colitis with negative PCR
Current guidelines for evaluation of diarrhea in solid-organ transplant recipients from the Infectious Disease Community of Practice of the American Society of Transplantation:
1. stopping any medications of non-immunosuppressive medications if possible.
2. Monitor CNI level and keep it on the lower level.
3. first-line microbiological testing including Clostridium difficile polymerase chain reaction (PCR), CMV PCR, and multiplex PCR if available.
4. Colonoscopy for detection of CMV tissue invasion with negative PCR and PTLD.
5. second-tier microbiological testing should include stool PCR for viral pathogen, ova, and parasite evaluation; giardia and cryptosporidium enzyme immunoassay; and breath test for bacterial overgrowth.
What is the most likely explanation for this patient’s diarrhoea?
How should this patient be managed?
1- Supportive therapy including intravenous fluids and correction of electrolytes disturbances
2- Symptomatic therapy including loperamide to decrease bowel motions
3- Modulation and monitoring of immunosuppression
· keeping CNI trough level at lower level.
· Shifting to enteric coated mycophenolate maybe beneficial.
· Close follow up of CNI level with possible of increase of the level because diarrhea associated with damage of P-glycoprotein.
4- Nitazoxanide can be used due to its antiviral effect.
Why mention IV fluids to begin with in everyone with post transplant diarrhoea?
I like that your suggestion of monitoring tacrolimus levels closely.
1. What is the differential diagnosis of diarrhoea following solid organ transplantation?
The most common causes of diarrhea in patients after transplantation include:
· Infectious diarrhea: infections; frequently attributed to Clostridium difficile, CMV, and norovirus.
· Non-infectious diarrhea as a result of immunosuppressive medications, with the highest incidence associated with mycophenolic acid
· Antibiotics.
2. What should be included in the diagnostic evaluation of posttransplant diarrhoea?
It is critical to evaluate the cause of diarrhea in a kidney transplant recipient, as identification of a specific etiology may allow for a focused treatment.
Current guidelines for evaluation of diarrhea in solid-organ transplant recipients from the Infectious Disease Community of Practice of the American Society of Transplantation recommend:
· Start with stopping any non-immunosuppressive medications that may cause diarrhea—such as proton pump inhibitors, H2 agonists, and oral hypoglycemics
· first-line microbiological testing including Clostridium difficile polymerase chain reaction (PCR), CMV PCR, and multiplex PCR if available.
· If these tests return negative results, second microbiological testing should include stool PCR for viral pathogen, ova, and parasite evaluation; giardia and cryptosporidium enzyme immunoassay; and breath test for bacterial overgrowth.
3. What is the most likely explanation for this patient’s diarrhoea?
For this patient, tacrolimus level was found to be within desired therapeutic limits (7 ng/mL) and first line microbiological testing was negative. Stool ova and parasite and stool culture were also negative.
Fecal multiplex PCR was positive for sapovirus infection.
4. How should this patient be managed?
· To date there have been no therapies shown to be effective in treating sapovirus infections.
· Previous reports have demonstrated symptom relief with intravenous fluids, antimotility agents such as loperamide, and reduction of immunosuppression to promote the immune system to clear the viral infection.
· Limited case studies have also suggested nitazoxanide as a potential therapeutic agent.
· This patient was managed with intravenous fluids and reduction of his mycophenolate dosage from 720 mg twice a day to 360 mg twice a day. This was associated with improvement of acute diarrhea and complete resolution of his acute-on-chronic diarrhea.
Why mention IV fluids to begin with in everyone with post transplant diarrhoea?
My caution: antimotility agents such as loperamide ONLY after excluding infectious cause .
I like that your suggestion of monitoring tacrolimus levels closely.
Differential diagnosis of diarrhoea following solid organ transplantation?
Diarrhea is a common post-transplant problem, with a 3-year cumulative incidence reported to be around 22%.
It has been linked to worse clinical outcomes, such as acute kidney damage (AKI), tacrolimus and mycophenolate levels that are over therapeutic ranges, and lower graft and patient survival.
Those who have undergone transplantation are most frequently affected by infections, immunosuppressive drugs, and antibiotics for diarrhea.
Immunosuppressive medications frequently cause non-infectious diarrhea in transplant recipients, with mycophenolic acid having the highest prevalence.
Significantly, compared to recipients of other solid organ transplants, individuals with combined kidney-pancreas transplants are more likely to have immunosuppression due to a higher risk of rejection.
The common causes of infectious diarrhea after kidney donation are Clostridium difficile, CMV, and norovirus.
Diagnostic evaluation of posttransplant diarrhoea?
It is crucial to determine the root of diarrhea in kidney transplant recipients since pinpointing the source may enable targeted treatment.
Stopping any non-immunosuppressive drugs that may cause diarrhea is the first step in the current American Society of Transplantation guidelines for evaluating diarrhea in solid-organ transplant recipients.
STOP proton pump inhibitors, H2 agonists,and oral hypoglycemics—and first-line microbiological testing including Clostridium difficile polymerase chain reaction (PCR), CMV PCR, and multiplex PCR
Second-tier microbiological testing should include stool PCR for viral pathogen, ova, and parasite evaluation; giardia and cryptosporidium enzyme immunoassay; and breath test for
bacterial overgrowth
Likely explanation for this patient’s diarrhoea?
The most likely diagnosis, given the positive stool PCR, is sapovirus infection, which causes abrupt exacerbation of chronic diarrhea.
Recent case reports indicate sapovirus infections causing patients to experience chronic, severe diarrhea following kidney transplants.
Together with norovirus, sapoviruses are single-stranded positive-sense RNA viruses that are not enclosed and do not belong to the Caliciviridae family.
Usually, a stool sample is tested using real-time PCR or multiplex PCR to make the diagnosis.
Patient management?
There are currently no treatments that have been demonstrated to be successful in treating sapovirus infections.
Past studies have shown that intravenous fluids, antimotility medications like loperamide, and a reduction in immunosuppression can all help relieve symptoms and encourage the immune system to fight off the viral infection.
Also, it’s important to keep an eye on tacrolimus levels since enterocyte damage can impair the P-glycoprotein efflux pump, which raises tacrolimus levels in the blood.
It is usual practice to reduce mycophenolate dosage in response to post-transplant diarrhea, and it has been demonstrated to be somewhat effective in patients with persistent diarrhea, regardless of the cause.
Why mention IV fluids to begin with in everyone with post transplant diarrhoea?
My caution: antimotility agents such as loperamide ONLY after excluding infectious cause .
I would suggest careful monitoring tacrolimus levels closely.
OK prof.
thaank you
What is the differential diagnosis of diarrhea following solid organ transplantation?
1. Infectious causes, including a) bacteria, such as Clostridium difficile, Campylobacter spp., Salmonella spp., bacterial overgrowth, Aeromonas spp., and Escherichia coli; b) viruses, such as Cytomegalovirus, Norovirus, Sapovirus, Rotavirus, Adenovirus, and Enterovirus; and c) parasites, such as Giardia, Crypto
Second, factors other than infections include: a) immunosuppressive drugs; B Immunosuppressive drugs: mycophenolate, tacrolimus, cyclosporine, and sirolimus Non-immunosuppressive drugs: antimicrobial, antiarrhythmic, anti-diabetic, laxative, proton pump inhibitor, and protease inhibitor are only a few examples.
Thirdly, besides GVHD, PTLD, and IBD, there are a few others: Colorectal cancer: malabsorption
What should be included in the diagnostic evaluation of posttransplant diarrhea?
Stool analysis and culture
Multiplex PCR testing of a stool sample for the viral pathogen, ova, and parasite evaluation; giardia and cryptosporidium enzyme immunoassay; and breath test for bacterial overgrowth.
putting an end to the use of non-immunosuppressive drugs, undergoing first-line microbiological testing, having a stool PCR done, as well as giardia and cryptosporidium enzyme immunoassays, and doing a breath test.
It was determined that the tacrolimus level was within the therapeutic limits, and the first-line microbiological tests came out negative.
A positive result for sapovirus was found in the fecal multiplex PCR.
CMV PCR.
What is the most likely explanation for this patient’s diarrhea?
This patient’s diarrhea is likely caused by a sapovirus infection.
Tacrolimus was within therapeutic limits.
Fecal multiplex PCR detected sapovirus. Stool ova, parasite, and culture were negative.
How should this patient be managed?
Sapovirus infections have no effective treatments. Intravenous fluids, loperamide, and immunosuppression lowering have been shown to relieve symptoms.
Intravenous fluids
F/U tacrolimus level
Nitazoxanide may potentially be a treatment.
reducing mycophenolate dose has been proven to help.
Switching to enteric-coated mycophenolate or azathioprine, which reduces posttransplant diarrhea risk, is another option.
Why mention IV fluids to begin with in everyone with post transplant diarrhoea?
My caution: antimotility agents such as loperamide ONLY after excluding infectious cause .
I like that your suggestion of monitoring tacrolimus levels closely.
IV fluids if the patient has a manifestation of dehydration and his oral intake can’t match the water deficit. we face these cases frequently(8-10 times per day) and the patient has AKI.
Yes Dr Weam, I agree
What is the differential diagnosis of diarrhea following solid organ transplantation?
A- Infectious diarrhea
B- Drug induced
C- Malignancy such as cancer colon, PTLD
D- Others including graft versus host disease, IBD, malabsorption
What should be included in the diagnostic evaluation of posttransplant diarrhoea?
Diagnostic work up should include
A- Routine investigations
B- Searching for the cause
What is the most likely explanation for this patient’s diarrhoea?
How should this patient be managed?
1- Supportive therapy including intravenous fluids for treatment of dehydration
2- Symptomatic therapy including lopramide to decrease bowel motions
3- Modulation and monitoring of immunosuppression
4- Some experts recommend the use of nitazoxanide due to its antiviral effect, but the evidence is limited
My caution: antimotility agents such as loperamide ONLY after excluding infectious cause .
What is the differential diagnosis of diarrhoea following solid organ transplantation?
1. Infectious causes:
a) Bacteria
· Clostridium difficile
· Campylobacter spp.
· Salmonella spp.
· Bacterial overgrowth
· Aeromonas spp.
· Escherichia coli
b) Viruses
· CMV
· Norovirus
· Sapovirus
· Rotavirus
· Adenovirus
· Enterovirus
c) Parasitic
· Giardia
· Cryptosporidium
· Isospora, Cyclospora
· Microsporidium
· Entamoeba
2. Non-infectious causes:
a) Immunosuppressive medications B Mycophenolate
· Tacrolimus
· Cyclosporine
· Sirolimus
b) Non-immunosuppressive medications
· Antibacterial
· Antiarrhythmic
· Antidiabetic
· Laxatives
· Proton pump inhibitors
· Protease inhibitors
3. Others:
· GVHD
· PTLD
· IBD
· Colon cancer
· Malabsorption
What should be included in the diagnostic evaluation of posttransplant diarrhoea?
1. Stopping any nonimmunosuppressive medications that may cause diarrhea.
2. Immunosuppression drug level.
3. first-line microbiological testing including Clostridium difficile polymerase chain reaction (PCR), CMV PCR, and multiplex PCR if available.
4. Second-tier microbiological testing should include stool PCR for viral pathogen, ova, and parasite evaluation; giardia and cryptosporidium enzyme immunoassay; and breath test for bacterial overgrowth.
What is the most likely explanation for this patient’s diarrhoea?
Sapovirus infection is the most likely explanation for this patient’s diarrhoea.
· Tacrolimus level was found to be within desired therapeutic limits (7 ng/mL).
· First- line microbiological testing was negative.
· Stool ova and parasite and stool culture were negative.
· Fecal multiplex PCR was positive for sapovirus.
How should this patient be managed?
1. Adequate hydration.
2. Antimotility agents such as loperamide.
3. Reduction or modification of immunosuppression to promote the immune system to clear the viral infection.
· Reducing mycophenolate dosage.
· Switching mycophenolic acid to an enteric-coated mycophenolate or azathioprine.
4. Tacrolimus levels should be closely monitored, as enterocyte damage can disrupt the P-glycoprotein efflux pump, leading to increased serum tacrolimus levels.
5. Nitazoxanide is suggested as a potential therapeutic agent(its efficacy is limited to case reports).
I like your list of very pragmatic comments:
Typing whole sentence in bold amounts to shouting.
III. Diarrhoea in a Patient with Combined Kidney-Pancreas Transplant
What is the differential diagnosis of diarrhoea following solid organ transplantation?
Etiologies of Diarrhea in Patients Posttransplantation:-
Infectious
Bacteria
Viruses
Parasitic
Noninfectious
Other
====================================================================
What should be included in the diagnostic evaluation of posttransplant diarrhoea?
===================================================================
What is the most likely explanation for this patient’s diarrhoea?
====================================================================
How should this patient be managed?
====================================================================
Final Diagnosis
Why mention IV fluids to begin with in everyone with post transplant diarrhoea?
My caution: antimotility agents such as loperamide ONLY after excluding infectious cause .
I like that your suggestion of monitoring tacrolimus levels closely.
Many thanks Prof.Sharma for your suggestions and counsel
Why mention IV fluids to begin with in everyone with post transplant diarrhoea?
I’m talking about managing fluids to prevent acute kidney injury
What is the differential diagnosis of diarrhoea following solid organ transplantation?
The most common causes of diarrhea in patients after transplantation include infections, immunosuppressive medications, and antibiotics
Infection
1. Bacteria: clostridium difficilea , campylobacter spp. , salmonella spp, bacterial overgrowtha , aeromonous spp, scherichia coli
2. Viruses: CMV, norovirus , sapobavirus , rotavirus , adenovirus
3. Parasitic: Giardia , Cryptosporidium , Isosopora Cyclospora , Microsporidium, Entameoba
Noninfection:
1. Immunosurpressive medications: MMF, tacrolimus, cyclosporine, sirolimus
2. Nonimmunosuppressive medications: antibacterial, antiarrhythmic, antidiabetic laxatives, proton pump inhibitors, protease inhibitors
Other
GVHD, PTLD, IBD, colon cancer, malabsorption, microscopiccolitis, malakoplakia
What should be included in the diagnostic evaluation of posttransplant diarrhoea?o Start with stopping any nonimmunosuppressive medications that may cause diarrhea (proton pump inhibitors, H2 agonists, and oral hypoglycemic)
o First-line microbiological testing including Clostridium difficile PCR, CMV PCR, and multiplex PCR if available
o If these tests return negative, second-tier microbiological testing should include stool PCR for viral pathogen, ova, and parasite evaluation; giardia and cryptosporidium enzyme immunoassay; and breath test for bacterial overgrowth
What is the most likely explanation for this patient’s diarrhoea?o sapovirus infection (Fecal multiplex PCR was positive for sapovirus)
o Sapoviruses are nonenveloped, single-stranded positive-sense RNA viruses that belong to the Caliciviridae family along with norovirus
o Diagnosis: real-time PCR or multiplex PCR testing of a stool sample
How should this patient be managed?o No effective treatment for sapovirus infections
o Supportive treatment with intravenous fluids, antimotility agents (loperamide), and reduction of immunosuppression
o Tacrolimus levels should be closely monitored, as enterocyte damage can disrupt the P-glycoprotein efflux pump, leading to increased serum tacrolimus levels
o Nitazoxanide (limited evidence)
o Immunosuppressions: reducing MMF, switching mycophenolic acid to an enteric-coated mycophenolate or azathioprine
Why mention IV fluid to begin with in everyone with post transplant diarrhoea?
I like your list of very pragmatic comments:
1-What is the differential diagnosis of diarrhoea following solid organ transplantation?
Infectious
Ø Bacteria :Clostridium difficile , Campylobacter , Salmonella , Bacterial overgrowth, Aeromonas , Escherichia coli
Ø Viruses: CMV ,Norovirus ,Sapovirus , Rotavirus ,Adenovirus , Enterovirus
Ø Parasitic: Giardia , Cryptosporidium ,Isospora, Cyclospora, Microsporidium ,Entamoeba
Noninfectious
Immunosuppressives as Mycophenolate , Tacrolimus , Cyclosporine , Sirolimus
Nonimmunosuppressive drugs as Antibacterial , Antiarrhythmic , Antidiabetic , Laxatives ,Proton pump inhibitors , Protease inhibitors
Other
GVHD ,PTLD ,IBD , Colon cancer , Malabsorption
2-What should be included in the diagnostic evaluation of posttransplant diarrhoea?
Guidelines include discontinuation of any non immunosuppressive medications as PPI or oral hypoglycemics .
Microbial evaluation by C difficile PCR, CMV PCR, and multiplex PCR if available ,if all are negative , second-tier microbiological testing should include stool PCR for viral pathogen, ova, and parasite evaluation; giardia and cryptosporidium enzyme immunoassay; and breath test for bacterial overgrowth.
-If there was fever with diarrhea or pathogenic bacteria or parasite detected for antibacterial therapy.
– If no pathogen detected or Norovirus or Sapovirus then for supportive hydration and antimotility if diarrhea persists then for immunosuppression adjustment, if turned into persistening chronic diarrhea so for breath test to exclude small intestinal overgrowth treated with antibacterial therapy if non conclusive then for upper and lower endoscopy with biopsy
-CMV viremia for ganciclovir or valganciclovir then for upper and lower endoscopy with biopsy if needed
-Malabsorption as PTLD ,IBD,bloody diarrhea, CMV D+/R- then for upper and lower endoscopy with biopsy
3-What is the most likely explanation for this patient’s diarrhoea?
-Sapovirus infection leading to acute deterioration of chronic diarrhea and it came positive in stool PCR test
– AKI
4-How should this patient be managed?
-Volume repletion either oraly if tolerating or intravenous in severe dehydration,
-antimotility agents such as loperamide after excluding infectious cause .
-reduction of immunosuppression by decreasing Mycophenolate dose from 720 mg BID to 360 mg BID or switching to enteric-coated mycophenolate or azathioprine, having lower risk of developing posttransplant diarrhea
– as well as monitoring tacrolimus levels closely.
I like your list of very pragmatic comments:
What is the differential diagnosis of diarrhoea following solid organ transplantation?
Infectious
•Bacteria; Clostridium difficile,Campylobacter spp, Salmonella spp, Bacterial overgrowth, Aeromonas spp and Escherichia coli
•Viruses: CMV, Norovirus, Sapovirus, Rotavirus, Adenovirus, Enterovirus
• Parasitic; Giardia, Cryptosporidium, Isospora, Cyclospora, Microsporidium, Entamoeba
Noninfectious
•Immunosuppressive medications; MMF, Tacrolimus, Cyclosporine, Sirolimus
•Non-immunosuppressive medications; Antibacterial, Antiarrhythmic, Antidiabetic, Laxatives, PPI and Protease inhibitors
•Other: GVHD, PTLD, IBD, Colon cancer and Malabsorption
What should be included in the diagnostic evaluation of posttransplant diarrhoea?
– First, to stop any non-immunosuppressive medications that may cause diarrhea.
– First line microbiological testing including: C. difficile PCR, CMV PCR, and multiplex PCR if available
– If previous first line tests were negative send for: stool PCR for viral pathogen, ova, and parasite evaluation; giardia and cryptosporidium enzyme immunoassay; and breath test for bacterial overgrowth.
– Additional consideration: EGD and colonoscopy with biopsy.
What is the most likely explanation for this patient’s diarrhoea?
Fecal multiplex PCR was positive for sapovirus. The most likely diagnosis is sapovirus infection resulting in acute worsening of chronic diarrhea and AKI.
How should this patient be managed?
– No effective therapy against sapovirus infection.
– Symptomatic and supportive therapy: IV fluids, and antimotility agents; loperamide
– Reduction of IS ; reduce MMF from 720 BID to 360 BID, or switch MMF to EC-MPS or azathioprine.
– Monitor graft function closely while reducing IS
– Careful monitoring for tacrolimus level.
– Nitazoxanid; antimicrobial agent evidence is limited to case report
IV fluid start specific to index patient how presented with severe diarrhea causing acute kidney injury.
I appreciate that anti-motility start after excluding other possible infectious causes.
DD of diarrhea following SOT
a) C.dificile.
b) Campylobacter spp.
c) Salmonella spp.
e) bacterial overgrowth.
f) Aeromonas spp.
g) E.coli.
a) CMV.
b) Norovirus.
c) Sapovirus.
d) Rotavirus.
e) Adenovirus.
f) Enterovirus.
a) Giardia.
b) Cryptosporidium.
c) Isospora, Cyclospora.
e) Microsporidium.
f) Entameaba.
2. Non-infectious
a) MMF.
b) TAC.
c) CyA.
d) SIR.
a) Antibacterial.
b) Antiarrhythmic.
c) Antidiabetic.
e) Laxatives.
f) PPIs.
g) Protease inhibitors.
a) GVHD.
b) PTLD.
c) IBD.
d) Colon cancer.
e) Malabsorption.
Diagnostic evaluation
The most likely cause of diarrhea in this patient
Management of the Saprovirus infection
Anti-motility (loperamide) to be given only after ruling out infective causes.
Yes, prof
thank you
What is the differential diagnosis of diarrhoea following solid organ transplantation?
a) Infectious cause-
b) Non-infectious cause
c) Other
What should be included in the diagnostic evaluation of posttransplant diarrhoea
If the above investigation comes back negative, then we do the following:
What is the most likely explanation for this patient’s diarrhoea?
It is acute on chronic diarrhoea in post-transplant patient precipitated by Sapovirus infection, and complicated by acute kidney injury
How should this patient be managed?
I admire your sensible clinical approach
I appreciate prof Ajay
Differential diagnosis of post transplant diarrhea:
(A) Infectious agents:
(B) Non infectious:
What should included in diagnosis evaluation of post transplant diarrhea?
What is the most likely explanation of this patient diarrhea:
How should this patient managed:
Why mention IV fluid to begin with in everyone with post transplant diarrhoea?
Anti-motility (loperamide that your have spelt incorrectly) to be given only after ruling out infective causes.
Why not start with oral fluid replenishment unless a patient can not tolerate oral or the fluid deficit is too much to be replaced orally.
There are instances when we could not reinstate the patient to MMF and azathioprine was not possible due to that patient being on allopurinol, we have used sirolimus.
IV fluid start specific to index patient how presented with severe diarrhea causing acute kidney injury.
Anti-motility start after diagnosis of saprovirus infection & excluding other possible infectious causes.
So nice of you, Dr Ban, to explain
1.What is the differential diagnosis of diarrhoea following solid organ transplantation?A. Infection
B. Non-infection
2.What should be included in the diagnostic evaluation of posttransplant diarrhoea?A. First step:
IF the first step is negative, then move to the
B.Second step: second-tier microbiological testing
3.What is the most likely explanation for this patient’s diarrhoea?
4.How should this patient be managed?
Why mention IV fluid to begin with in everyone with post transplant diarrhoea?
Anti-motility (loperamide) to be given only after ruling out infective causes.
Why not start with oral fluid replenishment unless a patient can not tolerate oral or the fluid deficit is too much to be replaced orally.
Prof, thank you
So nice of you, Dr Ben, to explain
Thnxs a lot prof