A recent retrospective study (R Levy et al. J Pediatr 2019; 209: 233-5) analyzed the musculoskeletal presenting manifestations of pediatric inflammatory bowel disease (IBD).
In their cohort of 715 patients with IBD, 137 had arthritis and/or arthralgia. 28 of these 137 patients (3.9% of total cohort) had arthritis preceding the diagnosis of IBD and were eligible for this study. Only 23 had complete data and were compared with 46 children with arthritis due to JIA (n=21), FMF (n=7), and postinfectious arthritis (n=18).
- Patients with subsequent IBD diagnosis were more likely to have sacroiliac involvement (34.8% vs. 2.2%), more likely to have anemia (mean hgb 10.5 vs 12), more likely to have low albumin (mean 3.5 vs 4.3) and to have higher inflammatory markers (ESR 81 vs 46; CRP 6.6 vs 4.5 mg/dL)
- In patients with calprotectin levels, 5 of 6 were >300 mg/kg and one was borderline
- On direct questioning at time of IBD diagnosis, prolonged gastrointestinal symptoms (e.g. abdominal pain, diarrhea, weight loss, aphthous ulcers) were evident in 78%.
- 4 of the 23 (17.3%) were diagnosed with IBD during the primary investigation. Ultimately, Crohn’s diagnosis was established in 87% of the IBD group.
My take: This study is important for pediatricians and rheumatologists. ~4% of children presenting with arthritis have IBD. Careful interrogation for GI symptoms (and perianal exam) will avoid diagnostic delay in most patients as would a stool calprotectin. Features like sacroileitis, and abnormal labs should also increase the suspicion for IBD.
Briefly noted: In a study discussing pediatrician beliefs about JIA (MR Pavo, J de Inocencio, J Pediatr 2019; 209: 236-9) there is an important caveat for GI doctors:
“It is clear that booster vaccinations against measles, mumps, rubella, or varicella zoster virus, can be considered in patients receiving < 15 mg/m-squared/week of MTX [methotrexate]” (Pediatr Rheumatol Online J 2018; 16: 46).
Related blog post:
- IBD Update Feb 2019 -last entry shows study indicating that patients with IBD and arthritis were more likely to require biologics.
El Retiro Park, Madrid
A recent study (S-M Haisma et al. Arch Dis Child http://dx.doi.org/10.1136/archdischild-2018-316584) shows that stool calprotectin levels stored at room temperature dropped nearly 20% after one day and dropped further over several days compared to baseline values, whereas calprotectin values remained reliable over six days for stool specimens stored at 4 degrees Celsius.
The authors conclude: “Calprotectin is not stable at room temperature. Children with IBD and their caretakers may be falsely reassured by low calprotectin values. The best advisable standard for preanalytical calprotectin handling is refrigeration of the stool sample until delivery at the hospital laboratory.”
Full text (link from KT Park’s twitter feed): Calprotectin instability may lead to undertreatment in children with IBD
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A small randomized, double-blind, placebo-controlled study (E Scaioli et al. Clin Gastroenterol Hepatol 2018; 16: 1268-75) examined the use of Eicosapentaenoic acid-Free Fatty Acid Form (EPA-FFA) a component of n-3 fish oil for patients with ulcerative colitis UC).
From 2014-2016, the investigators enrolled 60 patients who had partial Mayo score <2 and fecal calprotectin >150 mcg/g who had been receiving stable therapy for at least 3 months. Then they were randomized 1:1 to receive EPA 1000 mg BID or placebo for 6 months.
- 19 of 30 (63%) EPA-FFA group compared with 4 of 30 (13.3%) of placebo-treated group had achieved the primary endpoint of a 100-point reduction in fecal calprotectin at 6 months. OR 12.0, P<.001
- The secondary endpoint of clinical remission was noted in 23 of 30 (77%) in the EPA-FFA group compared with 15 of 30 (50%), OR 3.29, P=.035)
- No serious adverse effects were reported.
- Small number of patients from a single center
- Short follow-up
- In those without clinical relapse, a followup colonoscopy was not performed
My take: In this study EPA-FFA was associated with lower calprotectin and higher rates of remaining in remission. More data are needed.
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Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician. This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.
A recent study (I Weinstein-Nakar et al. Clin Gastroenterol Hepatol 2018; 16: 1089-97, editorial 1037-39)) provide data from 151 children who underwent multiple modalities to assess their Crohn’s disease (CD) (ImageKids Study group).
- MRE and ileocolonoscopy had concordance in 69% of cases. 55% had neither transmural nor mucosal healing, 14% had both transmural and mucosal healing.
- MRE did not show features of active disease in 25% that was identified on ileocolonoscopy. This is an expected finding given the ability of endoscopy (& capsule endoscopy) to identify milder mucosal lesions more precisely.
- MRE did show evidence of disease in 6% who had unremarkable ileocolonoscopy (mucosal healing)
- Calprotectin at a cut-off of 100 mcg/mL had 71% sensitivity and 92% specificity for diagnosing mucosal and transmural healing whereas a level of 300 mcg/mL had a sensitivity of 80% and specificity of 81%.
My take: This study confirms the complementary nature of cross-sectional imaging with endoscopy to determine healing. In addition, in children with CD, calprotectin levels of more than 100 mcg/mL could indicate the need for further assessment (if this would affect management).
This is in agreement with another recent post: IBD Reviews: Antibiotics and Biomarkers: “a calprotectin has a high level of excluding active inflammation/IBD. In populations with IBD, levels more than 250 mcg/g indicate a high likelihood of active inflammation whereas levels between 100-250 are indeterminate.”
Related blog posts:
Sunshine Meadows, Banff Nat’l Parke
A recent study (A Ricciuto et al. Clin Gastroenterol Hepatol 2018; 16: 1098-1105) provides more data regarding the lack of symptom correlation and inflammatory bowel disease (IBD) activity in children with primary sclerosing cholangitis (PSC).
In a prospective study of children with colonic IBD with and without PSC, the authors followed clinical features (eg. PUCAI), fecal calprotectin and endoscopy severity.
- Patients with PSC-IBD (n=37) in clinical remission had higher endoscopic scores and greater odd of active endoscopic disease than IBD-only controls (n=50) (odds ratio 5.9, with CI 1.6-21.5)
- Fecal calprotectin level <93 mcg/g were identified mucosal healing with 100% sensitivity and 92% specificity when compared with UC Endoscopic Index of Severity (UCEIS)
Overall, this study is in agreement with a prior adult study showing higher levels of active disease in those with PSC-IBD compared to those with IBD alone, despite clinical remission (Why does PSC increase the risk of colorectal cancer in UC?).
My take: Particularly in individuals with the combination of IBD-PSC, objective biomarkers (eg. Calprotectin) are needed to identify the accuracy of clinical remission; though, even in patients with IBD without PSC, objective biomarkers are needed as well due to the limitations of clinical symptom indices.
Related blog posts:
Moraine Lake, Banff
A clinical review, “Antibiotics in IBD: Still a Role in the Biological Era?” (O Ledder, D Turner, Inflamm Bowel Dis 2018; 24: 1676-88). While this article provides a detailed review of the use of antibiotics for Crohn’s (including perianal disease), Ulcerative colitis and the effects on the microbiome, the potential use for very early onset (VEO) IBD caught my attention:
“We have recently begun considering oral vancomycin and gentamicin as sole firstline therapy in the rare form of infantile (ie <2 years of age) mild to moderate IBD, with promising success…this is merely investigational” at this time. (Ref: Lev-Tzion R et al. Digestion 2017; 95: 310-13).
My take: Antibiotics can be a helpful adjunct therapy in both Crohn’s disease and Ulcerative colitis. It is unclear what role antibiotics will have for VEO-IBD.
A recent commentary (R Khanna et al, Inflamm Bowel Dis 2018; 24: 1619-23) examines the role of biomarkers. While much of this topic has been reviewed extensively, I found the part about calprotectin helpful. One of the topics with discrepant data has been the negative predictive value of calprotectin for detecting inflammatory bowel disease. The data in this review:
- From a meta-analysis in patients with symptomatic ulcerative colitis, calprotectin had a sensitivity of 0.88 and specificity of 0.79 compared to endoscopic inflammation. For Crohn’s disease, the respective values were 0.87 and 0.67.
- For histologic remission in ulcerative colitis, a study found that with a threshold of 155 mcg/g, calprotectin had a sensitivity of 78% and specificity of 71%.
- Another study suggested that values <100 mcg/g indicate quiescent disease, values 100-250 suggest possible active inflammation, and values >250 mcg/g suggest active inflammation.
- A cross-sectional study indicated that calprotectin ≥57 mcg/g had a sensitivity of 91% and specificity of 90% to identify endoscopically-active disease (Gastroenterol 2016; 150: 96-102)
My take: Sensitivity/specificity vary greatly based on the likelihood of disease; in populations at lower risk for IBD, a calprotectin has a high level of excluding active inflammation/IBD. In populations with IBD, levels more than 250 mcg/g indicate a high likelihood of active inflammation whereas levels between 100-250 are indeterminate.
Related blog posts:
A recent study (JF Colombel et al. Lancet 2017; http://dx.doi.org/10.1016/S0140-6736(17)32641-7 ) shows that “tight control” improves outcomes in Crohn’s disease. This study was alluded to in a previous post: CCFA 2017 Updates (part 2)
Background: The CALM study was an open-label, randomized study. 122 adult patients were randomized to typical clinical management and 122 patients received “tight control” in which treatment was modified by fecal calprotectin (≥250 mcg/g) and CRP (≥ 0.5 mg/dL) values in addition to clinical symptoms.
Treatment was escalated in both groups in a stepwise manner. Initial treatment was with adalimumab induction and then every other week. If patient did not meet treatment objectives, which differed in the groups, then adalimumab would be given every week, and then, if still needed, azathioprine would be added. Interestingly, both groups had ~25% of participants who were smokers which is known to worsen outcomes.
- Mucosal healing (CDEIS <4) was significantly improved in tight control group at week 48: 46% vs. 30%.
- Similarly, steroid-free remission based on CDAI <150 was better in tight control group compared with standard treatment at week 48: 59.8% vs. 39.3%. Endoscopic response was 50.8% compared with 40.2% respectively.
My take (1st part borrowed from authors): “Tight control of inflammation in patients with Crohn’s disease, with objective markers of disease activity and clinical symptoms to drive treatment decisions, achieved better endoscopic and clinical outcomes than conventional care based on symptoms alone.” Yet, there are a large number who do not respond adequately and better treatments in these patients are needed.
As an aside, these response rates based on objective markers are far lower than the remission rates claimed by ImproveCareNow; thus, while ImproveCareNow is forward-thinking and helping improve outcomes with inflammatory bowel disease, we need to be careful about citing remission rate trends that are not directly linked to objective markers.