Separating Celiac Disease From Non-celiac Gluten Sensitivity

SOURCE: Leonard MM, Sapone A, Catassi C, Fasano A. JAMA 2017;318:647-656.

The consequences of celiac disease include intestinal symptoms as well as diverse extraintestinal disorders such as anemia, osteoporosis, and increased risk of lymphoma. Gluten sensitivity has become sufficiently “popular” that an entire industry of “gluten-free” products has been created to satisfy the needs of a gluten-wary populace that too often views gluten as a toxin.

Patients with celiac disease possess specific human leukocyte antigen genotypes (DQ2 and DQ8) that allow an aberrant immunologic response to gluten-containing proteins, leading to the recognized signs and symptoms of celiac disease. Clinicians confirm the disease through intestinal biopsy. Consistently, this leads to not only symptom remission but also gluten antibody decline (anti-transglutaminase and antigliadin).

Anyone can experience a “food intolerance,” unpleasant symptoms ranging from dyspepsia to diarrhea and beyond in response to individual foods. Most patients who experience an adverse symptom in response to a particular food simply choose to avoid that food in the future and do not label it “broccoli sensitivity syndrome” or “lima bean sensitivity syndrome.”

Because adverse abdominal symptomatology is commonplace in otherwise healthy individuals periodically, and there is high public awareness of gluten as a cause of abdominal pain in celiac disease, some simply remove gluten from their diet after which adverse abdominal symptoms (or sometimes other symptoms) disappear. Many of these individuals believe they suffer from celiac disease and never undergo appropriate diagnostic testing to affirm the diagnosis.

As there is no diagnostic test to confirm any patient’s “non-gluten celiac sensitivity,” whether this clinical constellation should be considered a legitimate disorder remains a matter of controversy. However, there is no uncertainty about the necessity for long-term follow-up of patients with confirmed celiac disease.

BCG Vaccinations and the False-positive Effect

SOURCE: Mancuso JD, Mody RM, Olsen CH, et al. Chest 2017;152:282-294.

A placebo-controlled trial of bacille Calmette-Guerin (BCG) vaccination was performed among Native Americans from Alaska, Arizona, North Dakota, South Dakota, and Wyoming from 1935-1947. Varying opinions appear in the literature about the length of time during which prior BCG vaccination influences reactions to tuberculin skin testing. For instance, the CDC suggests that tuberculin cross-reactivity is unlikely to persist longer than 10 years post-BCG vaccination.

A publication by Mancuso et al offers us a 55-year follow-up of 3,151 subjects who received the BCG vaccines inclusive of up to 55 years post-BCG vaccination. In this population, within the first five years of follow-up, > 60% of BCG recipients registered positive tuberculin testing results.

Although this number waned somewhat over time (only 33% were positive after 50 years of follow-up), more than half of BCG vaccines remained tuberculin-positive throughout the initial 44 years of follow-up. Based on this data, clinicians should consider that the BCG vaccination effect could influence tuberculin testing responsivity for an essentially indefinite period.

Azithromycin Reduces Asthma Exacerbations

SOURCE: Gibson PG, Yang IA, Upham JW, et al. Lancet 2017;390:659-668.

In my early years of training, I was tempted occasionally to consider an antibiotic during an asthma exacerbation, but was quickly advised about the basic foolhardiness of such a consideration. After all, asthma exacerbations essentially are induced exclusively by viral infections (as well as thermal and atopic stimuli). Is it time to reconsider that posture?

In the AMAZES clinical trial, symptomatic adult asthmatics (n = 420) on a long-acting bronchodilator and inhaled steroid were randomized to azithromycin 500 mg thrice weekly vs. placebo for 48 weeks. The primary outcome was number of asthma exacerbations.

In a previous similarly designed trial of COPD patients receiving azithromycin 250 mg/day for one year, a decrement in hearing function was noted in the azithromycin treatment arm; hence, patients with any hearing impairment were excluded from this trial.

At 48 weeks, subjects on azithromycin experienced a 61% reduction in asthma exacerbations, as well as a statistically significant improvement in quality of life. Tolerability of azithromycin was very good, although diarrhea was twice as common in the azithromycin group as the placebo group (34% vs. 19%, respectively; P < 0.05).

The authors reminded us that macrolides, in addition to antibacterial effects, also possess anti-inflammatory and antiviral activity.