Category Archives: inflammatory bowel disease

More on IBD medicine risks

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As noted in a recent post (Assessing and discussing risk of lymphoma in IBD), diagrams can be useful to convey the absolute risks for IBD medicines; this risk is often poorly understood by patients and their families. Two articles add additional insight that may help with counseling. (Thanks to Ben Gold for forwarding these articles.)

  • Am J Gastroenterol 2012; 107: 964-70.
  • Am J Gastroenterol 2012; 107: 1051-63.

The first article reviews the risk of lymphoma with regard to inflammatory bowel disease treatment decisions.  Important points in this article include the following:

1. Relative risks may appear large while absolute risk may be quite low.  The estimate for absolute risk for lymphoma:

  • For azathioprine or 6-mercaptopurine: 1 additional case for every 4357 persons treated
  • For anti-TNF (infliximab, adalimumab, certolizumab): 1 additional case for every 2380 persons treated between ages 20-29.

2. Framing the discussion with regards to risk of continued active disease, continued exposure to steroids, and potential need for surgery can be helpful:

  • “It would take only three patients discontinuing their azathioprine to cause one additional relapse of IBD per year”
  • Seven patients stopping anti-TNF therapy would result in an additional hospitalization each year and 14 patients stopping anti-TNF therapy would result in an additional abdominal surgery each year
  • While the ‘relative risks of lymphoma associated with these medications may sound inappropriately large…A more appropriate comparison is the absolute risk of lymphoma versus the absolute risk of active/untreated disease or corticosteroid therapy.’  An example: if 2000 patients with IBD took one of these medications (eg. anti-TNF agent), probably one patient will develop a lymphoma; however, if none of those patients took an anti-TNF agent, it would result in more than 100 hospitalizations and nearly 60 surgeries.

3. “Patients can also be very sensitive to numerators and pay relatively insufficient attention to denominators.” This has been called “anchoring and adjustment” or “base-rate neglect.”  This issue has to do with “numeracy;” this is defined as the basic math skill needed for health-related activities. To help families, consider the following:

  • avoid labels such as “very low” when describing risk
  • use absolute risk data
  • use similar denominators when comparing risks
  • use visual aids

The second study cited is a pooled analysis of infections, malignancy, and mortality risks associated with infliximab and immunomodulator treatment in adult IBD patients.  This study collected safety data from 10 previous trials.  Five of these trials were randomized, controlled studies.  Table 3 and Table 4 detail extensive safety data for immunomodulators (eg. azathioprine) and for infliximab respectively.

With regard to immunomodulators, the combined studies enrolled 947 on immunomodulators in comparison to 1170 without immunomodulators.  With ulcerative colitis (UC) patients but not with Crohn’s disease (CD), immunomodulator use increased the risk of infections (120/100 patient years versus 92.5 among placebo-treated patients).  CD patients, but not UC patients, had an increased risk of malignancy with immunomodulator use (1.84/100 patient years compared with 0/100 patient years in the control group).  With the exception of the SONIC study, use of immunomodulator was not randomly assigned.  So, some of the increased risk in these patients could be due to having more severe IBD rather than due to the medication.

With regard to infliximab, and in contradiction to the previous article’s estimated risks, infliximab treatment did not appear to affect the incidence of infection, mortality, or malignancy.  This study and several others have not demonstrated an increased risk of malignancy with infliximab. This could be that even with this pooled data it is difficult to detect a rare adverse outcome.  More prospective studies and more long-term followup will be needed to truly determine the risk.

While it is known that these agents may increase the risk of some infections, the limited increase in infections which was detected only with immunomodulator use in UC is likely due to a lowered risk of infection when active inflammatory bowel disease is controlled.  A much bigger risk factor for infection is the use of corticosteroids.  When effective IBD medications are administered, this helps control inflammation and allows tapering of corticosteroids.

Related posts:

TNF-α antagonists and infections

Disease modifying treatment in IBD

Only one chance to make first impression

Delays in diagnosing Crohn’s disease

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Delayed diagnosis remains a problem in Crohn’s disease (Inflamm Bowel Dis 2012; 18: 496-505).  This study included a total of 1591 IBD patients (932 CD, 625 UC, 34 indeterminate colitis) from the Swiss IBD cohort study (SIBDCS).

  • Diagnostic delay in CD patients was significantly longer compared to UC patients (median 9 versus 4 months, P < 0.001).
  • 75% of CD patients were diagnosed within 24 months compared to 12 months for UC and 6 months for IC patients.
  •  Independent risk factors for long diagnostic delay in CD (>24 months)  included age <40 years at diagnosis (odds ratio [OR] 2.15, P = 0.010) and ileal disease (OR 1.69, P = 0.025)
  • In UC patients, nonsteroidal antiinflammatory drug (NSAID intake (OR 1.75, P = 0.093) and male gender (OR 0.59, P = 0.079) were associated with long diagnostic delay (>12 months)

Diagnostic delay has been a problem for quite a long time; in children, delays can worsen growth failure.  In 1988, Kanof et al reported that decreased height velocity preceded the diagnosis of CD in 88% of their patients (pediatric cohort). In addition, 42% of their population had a reduction in height velocity before intestinal symptoms were noted.

Especially when there is not a lot of colonic disease, a high degree of suspicion needs to be maintained.  This is not difficult for pediatric gastroenterologists.  For pediatricians and family physicians, the increased availability of biomarkers (Biomarkers identify patients who benefit and how) should be helpful in reducing diagnostic delays.

Additional blog entries and references:

  • Kanof ME, Lake AM, Bayless TM. Decreased height velocity in children and adolescents before the diagnosis of Crohn’s disease. Gastroenterology.1988; 95 :1523– 1527.
  • Differentiating ulcerative colitis from Crohn disease in children and young adults: report of a working group of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the Crohn’s and Colitis Foundation of America.  North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition, Colitis Foundation of America, Bousvaros A, Antonioli DA, Colletti RB, Dubinsky MC, Glickman JN, Gold BD, Griffiths AM, Jevon GP, et al.J Pediatr Gastroenterol Nutr. 2007 May; 44(5):653-74.

IL-10 and early onset IBD

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Among physicians who take care of patients with inflammatory bowel disease (IBD), there is an understanding that the labels “Crohn’s disease” (CD) and “ulcerative colitis” (UC) are imprecise labels.  There may be many subtypes of IBD that are classified as CD or UC.  This is becoming even more clear with advances in genetics which have shown specific genetic defects that predispose to an IBD phenotype.  In fact, more than 100 genetic loci have been uncovered that contribute to IBD, more than any other complex disease (according to editorial in same issue as reference below, pgs 285-87).

Immunodeficiency disorders, like chronic granulomatous disease, are well-recognized as potential mimics for IBD. More recently, IL-10 and IL-10 recpetor genetic mutations have been associated with early-onset IBD phenotypes (Gastroenterol 2012; 143: 347-55.)

In this study, 66 patients whose IBD started before age 5 were investigated for mutatons in the genes encoding IL-10, IL10R1, and IL-10R2.  IL-10R deficiency was confirmed with functional assays of patients’ mononuclear cells.  “Using a candidate gene sequencing approach, we identified 16 patients with IL-10 or IL-10R deficiency.”  In all 16 patients, the phenotype included refractory colitis with perianal disease; symptoms developed in the first three months of life in these 16 patients.  Five of these patients improved after hematopoietic stem cell transplantation with a median followup of 2 years.

Take-home message:

Test patients with infantile IBD for IL-10 and IL-10 receptor deficiency

Contact for IL-10 testing (free):

Karoline Fiedler, Clinical Research Coordinator, IBD Program, Toronto

karoline.fiedler@sickkids.ca

http://www.neopics.com

Crohn’s disease Differential Diagnosis:

  • Tuberculosis
  • Histoplasma
  • Sarcoidosis
  • Amebiasis
  • CMV
  • C. diff
  • Klebsiella oxytoca
  • Actinomycosis
  • Vasculitis (dermatomyositis, Wegener’s, SLE)
  • FMF
  • Allergic colitis
  • Hirschsprung’s
  • Autoimmune enteropathy
  • HIV
  • Chronic granulomatous disease
  • Glycogen storage dz, 1B
  • Hermansky-Pudlak syndrome
  • Wiskott Aldrich syndrome
  • NEMO (NF-kB essential modifier) deficiency
  • Leukocyte adhesion deficiency
  • SCID
  • Behcet’s
  • FELS/hemophagocytic lymphohistiocytosis
  • Typhlitis
  • HSP
  • Solitary rectal ulcer syndrome
  • Early-onset: IL10/IL10R deficiency, XIAP, ADAM17, NCF2 gene variant

Additional references:

  • -Gastroenterol 2012; 143: 347-55.  IL-10 signaling defects and IBD.
  • -Gut 2012; 61: 1028-35.  NCF2 gene variant and IBD.
  • -NEJM 2011; 365: 1502-408.  ADAM17 deletion and IBD.
  • -NEJM 2009; 361: 2033-45.  IL-10 receptor and IBD.
  • -JPGN 2010; 51: 690.  Discusses sarcoid (check angiotensin converting enzyme, CGD, Hermansky Pudlak)
  • -JPGN 2010; 50: 99.  Perianal dz in young children may be due to autoimmune neutropenia. -IBD 2008; 14: 1443.  phagocyte dysfunction.  Also, discusses Hermansky-Pudlak, GSD 1B, chronic granulomatous disease, Chediak-Higashi, leukocyte adhesion deficiency, cylic neutropenia, congenital neutropenia
  • -Clin Gastro & Hep 2009; 7: 1037.  MRI best study for perianal fistulas.
  • -JPGN 2006; 42: 405.  Vasculitis mimicking IBD.
  • -Pediatr 2008; 121:  447.  Consider chronic granulomatous disease -particularly if recurrent.  15-18% of CGD pts with perianal abscess.  Immunocompromised hosts at increased risk along with Crohn’s patients.  However, “vast majority” do not have underlying disease.  Can treat perianal abscess medicaly in otherwise healthy infants. (Peds 2007; 120: e548).  www.pediatrics.org/cgi/content/full/120/3/e548
  • -NEJM 2005; 352: 489-94.
  • -Gold B et al. NEJM 2003; 349 (26): 2541, Table 2

Previous related posts:

Add it to the list

Upper endoscopy useful for identifying Crohn’s disease

Serology in IBD

More on anti-glycan antibodies in Crohn’s disease

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As noted in recent blog entry (Serology in IBD), anti-glycan antibodies have some usefulness in inflammatory bowel disease.  More data on the utility of these antibodies is available in a study which examined the presence of these antibodies in both a pediatric and adult cohort (Inflamm Bowel Dis 2012; 18: 1221-31).

Anti-L, Anti-C, anti-chitobioside (ACCA), anti-laminaribioside (ALCA), anti-mannobioside and anti-Saccaromyces cervisiae (ASCA) antibodies were tested in 131 pediatric patients (59 CD, 27 UC, 45 controls) and in 728 adult patients (355 CD, 129 UC, 244 controls).  In this study, 78% of pediatric CD patients had at least one serological marker.  ASCA was most accurate for CD diagnosis; it was present in 63% of the pediatric cohort. 

Combined usage of these antibodies helped differentiate CD from UC.  While sensitivity for detecting CD was 78% with the presence of one serological marker, the presence of three (or more) markers increased the specificity to 93% (for CD compared to UC); however, the presence of this many markers occurred in only 28%. Increasing antibody levels also correlated with complicated CD behavior, CD-related surgery and ileal disease location.

Serology in IBD

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Serological antibodies against a number of antigens have shown some utility in differentiating inflammatory bowel disease (IBD) from non-IBD and in distinguishing Crohn’s disease (CD) from ulcerative colitis (UC).  A recent article evaluated 204 articles in a systematic review of these serological markers (Inflamm Bowel Dis 2012; 18: 1340-55).

The study has several useful tables and a long list of references.  In its Table 1, 10 serologies are listed with a range for prevalence in CD, UC, alternative GI conditions, and in healthy population.  Table 2 summarizes the data in terms of sensitivity, specificity, positive predictive value, negative predictive value for these antibodies in determining IBD from non-IBD.

With regard to specific antibodies, the review highlights 10 antibodies:

1. Anti-neutrophil cytoplasmic antibodies (ANCA).  Autoantibody directed against a constituent of neutrophil granules.  With IBD (especially UC), an atypical perinuclear (pANCA) staining pattern with indirect immunofluorescence and DNase-sensitive make this pattern different from ANCA due to vasculitis.

2-7. Anti-glycan antibodies –directed against cell wall microbes and reflect interaction between the immune system and glycosylated cell wall components of microbiota.

2. Anti-Saccharomyces cerevisiae (ASCA IgA and IgG) –antibodies directed against yeast cell wall.  While ASCA antibodies are commonly found in CD patients, 20-25% (or higher in some studies) of healthy relatives will test positive for these antibodies as well.  Approximately 6% of relatives of UC patients will be ASCA-positive.

3. Anti-laminaribioside carbohydrate IgG antibodies (ALCA) –antibodies directed against laminaribioside

4. Anti-chitobioside carbohydrate IgA antibodies (ACCA) –antibodies directed against chitobioside

5. Anti-mannobioside carbohydrate IgG antibodies (AMCA) –antibodies directed against mannobioside

6. Anti-L –antibodies directed against laminarin (large polysaccharide)

7. Anti-C –antibodies directed against chitin (large polysaccharide)

8. Anti-OmpC.  OmpC is a transport protein of E coli

9. Anti-I2.  I2 is a Pseudomonas-associated antigen

10. Anti-CBir1.  CBir1 is a bacterial flagellin antigen

Conclusions:

  • Serology has only limited value for the initial diagnosis of IBD.
  • Serology has ‘better value’ in differentiating CD from UC, though there is substantial variability in serologic responses in both diseases.  Probably, serology is most useful in unclassified IBD (IBD-U) in preoperative setting; serology may help predict risk of developing complications among patients undergoing pouch surgery.
  • Serology is useful in predicting a complicated disease course. The presence and magnitude of these antibodies are strong predictors of disease progression.

Additional references:

  • Pediatrics. 2010 Jun ;125 (6):1230-6.  Shortcomings of the inflammatory bowel disease Serology 7 panel. 
  • -Clin Gastro & Hep 2008; 6: 1105. Increased immune reactivity/markers associated with aggressive disease.
  • -IBD 2006; 12:1122. Expression of I2 antibodies (against a bacterial antigen of psedomonas fluorescens) was highly associated with clinical response to diversion. 15/16 with I2-pos had clinical response; 2/11 I2-neg had clinical response.
  • -IBD 2008; 14: S4 abstract 0010. Practical experience with IBD serology (n=90) much less accurate than reported by Prometheus: overall accuracy of 63% (vs 92%), 66% sensitivity (vs 93%), 59% specificity (vs 95%), 75% PPV (vs 96%), and 49% NPV (vs 90%). In this population, 34% of known IBD were incorrectly predicted. Of 32 who did not have any evidence of IBD after clinical investigation, 40% (13) were seropositive.
  • -Clin Gastro & Hep 2008; 6: 1105. Increased immune reactivity/markers associated with aggressive disease.
  • -IBD 2008; 14; 129. Serologic markers not very useful clinically.
  • -Pediatrics 2007; 119: e193. IBD serology performed poorly in comparison to combination of Hgb/ESR with regard to sensitivity (60% vs. 83%), specificity (92% vs. 96%), positive predictive value (60% vs. 79%) for IBD in children, n=227. Also one third of all positive serology in patients w/o IBD. The positive predictive value in patients w/o rectal bleeding was 35% vs 60% for routine tests.
  • -Gastroenterol 2006; 131: 366. antibodies against laminaribioside, chitobioside, and mannan have predictive value in detecting Crohn’s disease.
  • -Gastroenterol 2006; 130: 1078. Unaffected relatives positive for either OmpC or ASCA in 20% in large cohor (n=619 unaffected relatives. OmpC present in up to 44% of CD pts, up to 24% of UC pts, and 6% of controls.

Natural laws not patentable: the case with Prometheus

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While most individuals might think of greek mythology or the recent movie when hearing the word “Prometheus,” pediatric gastroenterologists might think of the company that performs a number of useful diagnostic tests.  Recently, Prometheus has had a legal setback (NEJM 2012; 365: 2338-40). 

Since the 1990s, Prometheus has tested for azathioprine (& 6-mercaptopurine) metabolites.  A therapeutic level of 6-thioguanine (6-TG), a metabolite for these drugs, is recognized as generally between 230-400 pmol per 8×10(to the 8th) red cells.  Levels outside this range often require drug adjustments.

When the Mayo clinic started to offer a slightly different assay, priced 25% below Prometheus’s test, Prometheus sued for patent infringement.  The court held that “if a law of nature is not patentable, then neither is a process reciting a law of nature;”  hence, Prometheus’s patent was rejected.

There are implications of this lawsuit on the use of a large number of biomarkers.  For example, patents for BRCA DNA sequences that increase the risk for cancer will probably be overturned.  Industry groups argue that denying patents will halt progress as companies will not be able to recoup investments in biomarker development.  Congress could consider passing laws allowing exclusive marketing of these innovations.  Alternatively, adequate funding through the NIH (National Institutes of Health) could allow development of biomarkers without the need for patents; in fact, 100 projects are in progress at this time.

Assessing and discussing risk of lymphoma in IBD

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A recent article has shown that the absolute lymphoma risk from medications in children and young adults with IBD is quite low (Inflamm Bowel Dis 2012; 18: 838-43).

In this single center study from 1979-2008, 1374 pediatric IBD patients had charts reviewed to determine whether lymphoma developed.  In total, two male patients who had received thiopurines developed lymphoma (one Hodgkin, one anaplastic large cell) in 6624 patient-years of follow-up.  Both patients are alive after chemotherapy.  Mean follow-up was 4.8 years per patient.  The absolute lymphoma incidence rate was 3 per 10,000 patient-years; after thiopurine exposure, the rate was 4.5 per 10,000 patient-years compared to an expected 0.58 per 10,000 patient-years.

In this study, 22% of the patients had received TNF inhibitors.  None developed lymphoma.  The risk of biologics could not be fully assessed due to a limited study period: 713 person-years taking the medication.

The risk of thiopurine-associated lymphoma was similar to previous studies but did not reach statistical significance.  As related in other studies, the risk of biologic agents, like Remicade, Humira, and Cimzia, is heavily influenced by whether patients had also received immunomodulators.

One useful way to try to convey this risk has been with diagrams.  One useful diagram is a palette of one thousand people or of 10,000 people showing the absolute risk and one showing the risk for other complications like infection.  You can make your own by going to the following link:

Download Communication Tools

RiskComm

Additional references/blog entries:

Only one chance to make first impression

Biologics | Living Longer | Arthritis Today Magazine -From Arthritis magazine: biologics improve survival in Rheumatoid arthritis

TNF-α antagonists and infections

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In our pediatric patients who receive tumor necrosis factor-α (TNF-α) antagonists, fortunately we see few infectious complications.  In older patients, infections are much more important source of morbidity.  The main TNF-α inhibitors in clinical use include infliximab, etanercept, adalimumab, and certolizumab. Two large studies help quantify this risk:

  • Grijalva CG et al. JAMA 2011; 306: 2331-39.
  • Strangeld A et al. Ann Rheum Dis 2011; 70: 1914-20.

The first study assembled retrospective cohorts between 1998-2007 with rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and psoriasis/psoriatic arthritis or ankylosing spondylitis (group 3).  This study’s acronym is SABER: Safety Assessment of Biologic Therapy. This data was compiled from 4 large US automated databases.  In total, there were 10,484 RA, 2323 IBD, and 3215 group 3 patients.  1172 serious infections were identified, mostly (53%) pneumonia or skin/soft tissue infections.  Among IBD patients, hospitalization rates were 10.91 (per 100 person-years) for TNF-α antagonists and 9.6 for comparison group.  The rates of hospitalization were similar in RA (8.16 with TNF-α antagonists) and lower in the group 3 patients (5.41 with TNF-α antagonists).   In all groups, baseline glucocorticoid use was associated with a dose-dependent increase in infections.  Overall, there was not an increase risk of hospitalizations with TNF-α antagonists compared with nonbiologic treatments.

The second cited reference examined patients from Germany with RA, enrolled in the RABBIT registry.  Data was available for 5044 patients.  There were 392 serious infections in this cohort with fewer infections noted after 3 years.  Risks for infection included age (>60), chronic lung or renal disease, history of serious infections, and treatment with glucocorticoids.  Treatment with 7.5-14mg conferred at relative risk (RR) of 2.1; treatment with ≥15mg conferred a RR of 4.7.  The rates of serious infections has an exponential change when risk factors are added together.  In Figure 3, estimated risk of serious infections for patients receiving ≥15mg  glucocorticoids along with three additional risk factors was 45% per year; with two risk factors the risk was approximately 20% and with one additional risk factor approximately 10%.

While these studies confirm significant risks of infections with biologic agents, the absolute risk is low particularly when other risk factors are not present.  In pediatric populations, glucocorticoids are the most prominent risk factor.  In addition, the risk of serious infections may be reduced by effective therapy.  In the SONIC study, serious infectious complications were less frequent in patients on combination therapy (infliximab and azathioprine) than with either monotherapy.  This result was likely due to the decreased need for glucocorticoids.

Additional references/relevant previous blogs:

  • NEJM 2010; 362: 1383. Sonic study. Combination AZA/IFX with greater efficacy. 56.8% remission in combo Rx.
  • -IBD 2008; 14: 721.  Pneumocystis jiroveci (carinii) w infliximab -review of 84 cases.  Dig Dis Sci 2007; 52: 1481-84.  PCP most likely to occur on average 3 weeks after 2nd infusion (possibly due to concommitant drug use)
  • -Gastroenterology 2008; 134: 929.  n=100 consecutive IBD patients with opportunistic infections.  Any of drugs associated w ~2.9 OR in adutls (greatest in >50yrs).  OR 14.5 when multiple immune drugs. Steroids more associated with Candida. AZA/6MP more with viral: HSV, VZV (shingles), CMV.  IFX less commonly with infections -though increased histoplasma and atypical mycobacterium
  • -Gastroenterology 2009; 136: 1182.  Review of biologics.
  • -IBD 2007; 13: 769.  Review of safety of wide range of biologics
  • –Clin Gastroenterol Hepatol. 2006; 5:621-30.  TREAT registry.  Steroids but not biologics associated with increased mortality risk.
  • Only one chance to make first impression

Upper endoscopy useful for identifying Crohn’s disease

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In a large pediatric study, the value of upper endoscopy in detecting Crohn’s disease (CD) is evident (JPGN 2012: 54: 753-57).

While the majority of pediatric patients with suspected inflammatory bowel disease probably undergo both upper endoscopy and colonoscopy, the added value of upper endoscopy remains unclear.  In this retrospective study with 171 pediatric patients (70 with CD, 33 with UC, 68 Non-IBD), 11% of children with CD had the diagnosis established based “solely” on the finding of granulomatous inflammation in upper intestinal tract (along with clinical symptoms).

Other key findings:

  • Presence of histologic gastric inflammation in CD patients compared to control patients was significantly higher (p<0.0001) but not significantly higher compared to UC patients (p=0.19).
  • Duodenal inflammation was highly suggestive of CD compared with both UC and non-IBD patients.  This occurred in 19% of CD patients compared with 0% and 1% in the other groups respectively.
  • 21 children (30%) had granulomas identified in upper GI tract (19 in stomach).  In 8 (11%), the diagnosis was changed based on this finding.  Prior to histology, the tenative diagnosis: 2 UC, 4 IC, 2 non-IBD.
One curious finding was a the presence of “perianal abscess/fistula” with similar frequency in CD patients and UC patients based on their Table 2 Patient Characteristics.
Additional references:
  • -IBD 2009; 15: 1101-4.  Presence of UGI disease in IBD.
  • -JPGN 2007; 44: 653.  NASPGHAN report on discriminating/labelling UC vs. Crohn’s.
  • -JPGN 2002; 35: 636-40. Advocates panendoscopy for all new IBD.  Granulomas in 28% of EGDs & 71% of UC pts c some abnl on EGD; 82% Crohn’s c abnl EGD.
  • -JPGN 2005; 41: abstract 181 (page 549).  UGI identified granulomas in 15% that were not identified elsewhere.
  • -JPGN 2004; 39: 257-61. Diagnostic role of EGD for pediatric IBD.
  • Magnetic resonance enterography for Crohn’s disease

Colonic disease and PSC

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While primary sclerosing cholangitis (PSC) has been associated with inflammatory bowel disease, and ulcerative colitis (UC) in particular, the pathogenesis of this relationship has not been established.  A fascinating observation on this relationship is that an inflamed colon is important in PSC development (Clin Gastroenterol Hepatol 2012; 10: 439-41).

In this study which reviewed 2754 Irish patients with IBD, 59 (2.2%) had PSC.  PSC incidence correlated with increasing colonic involvement.  Among the 13 patients with Crohn’s disease, none had isolated small bowel disease.  The second part of the study involved a review of 82 separate PSC patients attending the Irish National liver transplant unit.  The majority of ulcerative colitis patients had a pancolitis; all 10 PSC patients with Crohn’s disease had colonic involvement.

Since PSC occurs without IBD, colonic inflammation is not necessary for PSC development.  However, in patients with IBD, colonic inflammation is very important.  In fact, in a previous study of 53 PSC-IBD patients, no UC patient status post a colectomy had recurrent liver disease following liver transplantation whereas seven patients with intact colons had recurrent disease following liver transplantation.

The authors speculate that bacterial translocation along with subsequent portal bacteremia may be an important step in pathogenesis among these patients.

Additional references/previous posts: