Monthly Archives: November 2017
>99% Accuracy in Non-Biopsy Diagnosis of Celiac Disease
Another large study (KJ Werkstetter et al. Gastroenterol 2017; 153: 924-35) shows a high accuracy of diagnosing celiac disease (CD) without a biopsy when very high celiac titers are identified in symptomatic patients. A previous study (n=898) this year also showed similar findings: The Non-Biopsy Diagnosis of Pediatric Celiac Disease
The current study (2001-2014) identified 743 consecutive pediatric patients with positive celiac serology (TTG-IgA). Key findings:
- If TTG-IgA was higher than 10-fold the upper limit of normal and a separate sample tested positive for endomysial antibodies, then non-biopsy approach had a positive predictive value >99.6%. The authors utilized a variety of TTG-IgA assays.
- The authors noted that HLA-DQ2/DQ8 typing did not improve the accuracy of CD diagnosis. “Negative results for HLA-DQ2/DQ8 in patients with TGA or EMA positivity are most likely false negative …or due to very rare risk-allele combinations not recognized by the test systems.”
- “At least 50% of affected children in clinical practice will benefit from this nonbiopsy approach, which reduces burden and risks of endoscopy and anesthesia” and is more cost-effective.
The authors’ conclusion: “allowing omission of biopsies enables a correct diagnosis of CD in symptomatic children if TTG-IgA exceed 10xULN and positive EMA-IgA confirms celiac disease autoimmunity in a second blood sample. If one of these criteria is not fulfilled, biopsy should be performed to confirm the diagnosis.”
My take: This study provides convincing data that CD diagnosis does NOT require an intestinal biopsy under specific conditions.
Related blog posts:
- Followup Biopsies in Pediatric Celiac Disease?
- How Slow Do Objective Markers of Celiac Change After Treatment? | gutsandgrowth
- Are followup biopsies necessary in celiac disease? Look beyond the headlines
- To biopsy or not to biopsy -that is the question (for Celiac disease)
- How Accurate is Serology at Predicting Mucosal Healing in Celiac Disease
- Drug Therapy for Celiac Disease | gutsandgrowth
- Why is Celiac Disease Becoming More Prevalent? | gutsandgrowth
- Benefits of Gluten–Free Diet for “Asymptomatic” Celiac | gutsandgrowth
- Closer followup for Celiac disease & pediatric … – gutsandgrowth
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.
The MH Score: Separating primary Hemophagocytic Lymphohistiocytosis from Macrophage Activation Syndrome
“Sincerity is the key to success. Once you can fake that, you’ve got it made.”
–Groucho Marx
The above quote is not particularly related to this blog post –but I like it.
A recent study (F Minoia et al. J Pediatr 2017; 189: 72-8) provides data supporting a scoring system which helps distinguish primary hemophagocytic lymphohistiocytosis (HLH) from macrophage activation syndrome (MAS).
Background: “By convention, secondary HLH seen in rheumatic disorders is termed macrophage activation syndrome…occurs most commonly in systemic juvenile idiopathic arthritis (sJIA).” Both HLH and MAS are life-threatening, though HLH tends to be more severe. The treatment for the two disorders is much different.
HLH typically develops in the first year of life, though some remain asymptomatic until later. Identification of pathologic mutations (primary HLH is not a single disease) is considered the gold standard, but this “takes weeks to complete and is not available in many resource-limited areas.”
In this study, the authors reviewed clinical features from 362 patients with MAS and 258 patients with HLH to develop a scoring system that more readily distinguished these conditions.The data from 80% of the patients was used to construct the scoring system and then this was validated with the remaining 20%. MH Score:
- Age of onset, years: 0 points if >1.6 yr, 37 points if ≤1.6 yr
- Neutrophil count, x 10 to the 9th/L: 0 points if >1.4, 37 points if ≤1.4
- Fibrinogen, mg/dL: 0 points if >131, 15 points if ≤131
- Splenomegaly: 0 points if no, 12 points if yes
- Platelet count, x 10 to the 9th/L: 0 points if >78, 11 points if ≤78
- Hemoglobin, g/dL: 0 points if >8.3, 11 points if ≤8.3
The age of onset and severe neutropenia are weighted the most heavily as they most heavily influence the odds ratio of having HLH; with multivariate analysis (Table 3), age of onset ≤1.6 yrs had an OR of 40.3, and neutrophil count ≤1.4 had an OR of 39.3. All of the other parameters had OR between 2.9 and 4.4. Hepatomegaly favored HLH as well but was not independently associated with the diagnosis.
How to use this scoring system:
- In this cohort, the MH score ranged from 0 to 123. The median value was 97 for HLH and 12 for MAS.
- A cutoff of ≥60 yielded a sensitivity of 91% and specificity of 93% for the diagnosis of HLH. Higher values increased the probability of HLH further.
Most laboratory studies were more abnormal with HLH; however, both ferritin elevation and LDH elevation were more pronounced with MAS. Median ferritin was 5353 with MAS and 2910 with HLH. Median LDH was 1230 with MAS compared with 696 with HLH.
This study validated the MH score for distinguishing HLH from MAS associated with sJIA; this can allow early introduction of aggressive treatment and appropriate genetic/immunologic evaluation. The applicability of the MH score for distinguishing HLH from other conditions is unclear. Further prospective evaluation of the MH score is needed.
My take: This is a very helpful study and is likely to influence diagnostic workup and management of these sick patients. Due to the liver and spleen abnormalities, pediatric gastroenterologists need to be able to recognize both HLH and MAS.
Related blog post:
- Hemophagocytic Lymphohistioctosis: Advances | gutsandgrowth
- Diagnosing hemophagocytic lymphohistiocytosis … – gutsandgrowth
What’s with $1040 -is a fine of $40 more going to make a difference?
Breastfeeding: Protection from Inflammatory Bowel Disease
, et al. Systematic review with meta-analysis: breastfeeding and the risk of Crohn’s disease and ulcerative colitis. Aliment Pharmacol Ther. 2017;46:780-789.
https://doi.org/10.1111/apt.14291Thanks to Mike Hart for this reference.
Results
A total of 35 studies were included in the final analysis, comprising 7536 individuals with CD, 7353 with UC and 330 222 controls. Ever being breastfed was associated with a lower risk of CD (OR 0.71, 95% CI 0.59-0.85) and UC (OR 0.78, 95% CI 0.67-0.91). While this inverse association was observed in all ethnicity groups, the magnitude of protection was significantly greater among Asians (OR 0.31, 95% CI 0.20-0.48) compared to Caucasians (OR 0.78, 95% CI 0.66-0.93; P = .0001) in CD. Breastfeeding duration showed a dose-dependent association, with strongest decrease in risk when breastfed for at least 12 months for CD (OR 0.20, 95% CI 0.08-0.50) and UC (OR 0.21, 95% CI 0.10-0.43) as compared to 3 or 6 months.
From associated editorial by David Rakel:
This meta-analysis of 35 studies shows that there is a dose–response protective effect of the duration of breastfeeding on inflammatory bowel disease. The association shows as much as an 80% reduction in risk for both Crohn’s disease and ulcerative colitis for breastfeeding more than 12 months.
Inflammatory bowel disease arises from a complex set of interactions related to genetic susceptibility, environmental exposures, and a dysregulated immune response to dysbiotic intestinal microbiota, according to the study authors. These data will give us one more reason to encourage breastfeeding, ideally for a year or more.
Related blog post: Nutrition Week (Day 7) Connecting Diet and Epidemiology in IBD
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