Tag Archives: diagnosis

Metabolite Spectroscopy As a Diagnostic Tool for Autoimmune Hepatitis

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A Dimou et al. Hepatology 2024; 80: 266-277. NMR-based metabolomic signature: An important tool for the diagnosis and study of pathogenesis of autoimmune hepatitis

Methods: The authors examined treatment-naive patients with well-established AIH and compared them to healthy controls and those with other liver diseases.

Key Finding:

  • Fifteen metabolites (out of a total of 52 analyzed) differentiated AIH from disease controls (PBC+chronic viral hepatitis+metabolic dysfunction–associated liver disease) (95% sensitivity and 92% specificity)

In their discussion, the authors review the metabolism of the various metabolites and why they may be altered in AIH. “Our study found that cirrhosis did not seem to affect our results.” In ongoing studies, the authors are trying to determine how these metabolites change with treatment and whether they could be a predictive marker.

My take: Metabolite measurement could be helpful in the diagnosis of AIH as “NMR technology dose not need much sample handling, is highly reproducible, and with low costs.

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ESPGHAN Guidelines for Diagnosing Coeliac Disease 2020

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Briefly noted: S Husby et al. JPGN 2020; 70: 141-56.

Link to document: ESPGHAN Guidelines for Diagnosing Coeliac Disease 2020

Key recommendations for diagnosing celiac disease (CD):

  • If CD is suspected, measurement of total serum IgA and IgA-antibodies against transglutaminase 2 (TGA-IgA) is superior to other combinations
  • We recommend against deamidated gliadin peptide antibodies (DGP-IgG/IgA) for initial testing
  • Only if total IgA is low/undetectable, an IgG-based test is indicated
  • If TGA-IgA is ≥10 times the upper limit of normal (10× ULN) and the family agrees, the no-biopsy diagnosis may be applied, provided endomysial antibodies (EMA-IgA) will test positive in a second blood sample. HLA DQ2-/DQ8 determination and symptoms are not obligatory criteria
  • In children with positive TGA-IgA <10× ULN at least 4 biopsies from the distal duodenum and at least 1 from the bulb should be taken

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P’tit Train du Nord Linear Park

Best Approach for Identifying Eosinophilic Esophagitis

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A recent study (K Radicic, RF Stokes. Clin Gastroenterol Hepatol 2019; 1408-9) indicated that taking biopsies from three esophageal areas (proximal, mid, and distal)  improved the likelihood of identifying eosinophilic esophagitis (EoE).

Key findings:

  • In their study, among 96 patients with EoE, 55.2% were positive (>15 eos/hpf) in only 1 of the 3 levels.
  • 17 patients (17.7%) were positive in the mid-esophagus alone, and 6 patients (6.3%) were positive in the proximal esophagus alone.

The authors state that a 2-level biopsy protocol missed the diagnosis of EoE in roughly 1 of 5 patients.

My take: This study is provocative. However, the reasons why 3 levels improved their yield could be related to other factors rather than location.

  1. Prior studies have shown higher yield when taking 5 or 6 biopsies rather than fewer biopsies; thus, the location of biopsies may not be as important as the number of specimens
  2. Prior studies have shown that having another pathologist review the slides can increase the yield by ~20%; this indicates that careful review of specimens by itself is helpful.  Perhaps, more specimen containers will increase the time that a pathologist reviews the biopsies.

My view is that if adequate numbers of biopsies are taken from several locations, a single jar for all the specimens should suffice (& reduce costs) –though a formal study could be beneficial to confirm this.

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From NASPGHAN 2014 EoE Slide Set

Clostridium difficile Guidelines

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Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA)

L Clifford McDonald Dale N Gerding Stuart Johnson Johan S BakkenKaren C Carroll Susan E Coffin Erik R Dubberke Kevin W Garey Carolyn V GouldCiaran Kelly … 
Clinical Infectious Diseases, Volume 66, Issue 7, 19 March 2018, Pages e1–e48,https://doi.org/10.1093/cid/cix1085

Summary from Infectious Disease Advisor: Updated C difficile Infection Clinical Guidance From IDSA/SHEA

The comprehensive clinical practice guideline …was endorsed by the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA)…

Recommendations for treatment of CDI in adults… now favors a 10-day course of vancomycin or fidaxomicin rather than metronidazole for first-line therapy of mild/moderate CDI in adults… Fidaxomicin, also a newly recommended first-line therapy for mild/moderate CDI in adults, may reduce the risk for recurrent CDI because of its narrow spectrum compared with vancomycin.

Recommended treatment strategies for recurrent CDI, a complication that occurs in approximately 25% of patients, have also been revised…Following initial CDI treated with a 10-day course of vancomycin, either a several-week tapered and pulsed course of vancomycin or a 10-day course of fidaxomicin is recommended. For most patients, probiotics can be considered because of favorable cost and safety, although definitive efficacy data for probiotics to prevent recurrent CDI are still lacking. For multiply recurrent CDI (ie, at least 3 CDIs), correction of the patient’s underlying intestinal microbiota perturbation with fecal microbiota transplantation (FMT) should be strongly considered..

The diagnosis of CDI… Molecular tests (eg, nucleic acid amplification tests [NAATs], such as polymerase chain reaction), which do not differentiate colonization and infection, are now the most commonly used test for CDI among US hospitals. NAATs have the potential to misdiagnose patients with colonization as having CDI, particularly when used in patients with low likelihood of CDI. Thus, this guideline strongly reinforces the importance of practicing good diagnostic stewardship and limiting C difficile testing to patients with new-onset, unexplained, and clinically significant (ie, at least 3 unformed stools in a 24-hour period) diarrhea…formed stools should not be tested for C difficile, nor should patients be retested within 7 days of a previous negative C difficile test. In pediatric populations, because of the unclear role of C difficile as a cause of diarrhea in infants, children less than 12 months of age should not be tested…

If diagnostic stewardship is not an achievable goal, use of NAAT alone is likely to lead to frequent misdiagnosis of CDI among patients with C difficile colonization. In these cases, NAAT alone should be avoided and a multistep algorithm that incorporates toxin testing is recommended.

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Cumberland Island 2018

Complexity in Cystic Fibrosis Diagnosis

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The availability of multiple diagnostic techniques for cystic fibrosis has increased the complexity and created areas of uncertainty.  A recent supplement (J Pediatr 2017; 181S: 1-55) delve into these issues.

“The diagnosis of CF has become increasingly complex, as CFTR mutations resulting in a wide spectrum of dysfunction have been increasingly identified.”

On page S6, 27 consensus recommendations are given.

The article S45-51, reviews cystic fibrosis transmembrane conductance regulator-related metabolic syndrome (CRMS) and cystic fibrosis screen positive, inconclusive diagnosis (CFSPID).  Key points:

  • CRMS and CFSPID are equivalent entities with CRMS being the preferred terminology in the US
  • CRMS/CFSPID are relatively frequent; for every 3 to 5 cases of CF, there is one case of CRMS/CFSPID.
  • The majority of CRMS/CFSPID do NOT develop CF. Approximately 10-20% develop clinical features concerning for CF.

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The Push to Improve Diagnosis

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The Institute of Medicine’s (now called the National Academy of Medicine) “Improving Diagnosis in Health Care” (the link includes a link to a 1-hour briefing) is receiving a lot of attention. One recent commentary (H Singh, ML Graber. NEJM 2015; 373: 2493-95) elaborates on this issue. The IOM reports notes that “diagnostic errors affect at least 1 in 20 U.S. adults in outpatient settings each year, or 12 million adults per year.”

The report recommends “strengthening teamwork, reforming the teaching of diagnosis, ensuring that health information technology (IT) supports the diagnostic process, measuring and learning from errors in real-world practice, promoting a culture of diagnostic safety, reforming the malpractice and reimbursement systems, and increasing research funding.”

My take: This report highlights an enormous challenge for the healthcare system.  While IT support in theory sounds like it could help, right now IT isn’t helping much.  Many physicians are bogged down inputting data and trying to find enough time for critical thinking.  There is a lot of work ahead.