Prenatal exposure to acid suppressant medications and risk of allergen sensitization

In conclusion, in a cohort of children with a history of severe bronchiolitis those exposed to ASM prenatally are not at increased risk of developing food or environmental allergen sensitization by early childhood. The mechanism by which ASM exposure increases risk of childhood asthma remains unclear, but alterations in the gut microbiome merit consideration.

IL-31 uncouples skin inflammation from itch sensation in allergic dermatitis

Despite a robust literature associating IL-31 with pruritic inflammatory skin diseases, its influence on cutaneous inflammation and on the interplay between inflammatory and neurosensory pathways remain unmapped. Here, we examined the effects of IL-31 and its receptor IL31RA on both inflammation and pruritus in mouse models of dermatitis, including chronic topical house dust mite (HDM) exposure. Unexpectedly, Il31 deficiency increased cutaneous adaptive type 2 cytokine-producing cells and serum IgE. In addition, M2-like macrophages capable of fueling feedforward pro-inflammatory loops were selectively enriched in Il31ra-deficient skin. Thus, IL-31 is not strictly a pro-inflammatory cytokine, but rather an immunoregulatory factor that limits the magnitude of allergic skin inflammation. In contrast, Il31-deficient mice displayed a deficit in HDM-induced scratching. Itch reduction occurred despite intact - and in some cases increased - responsiveness of sensory neurons to other pruritogens released during HDM challenge, highlighting the non-redundant contribution of IL-31-receptive sensory afferents to pruritus in environmental allergen-induced dermatitis. When present, therefore, IL-31 uncouples circuits driven by sensory neurons and immune cells that converge in inflamed skin.

Genetic priming of sensory neurons in mice that overexpress PAR2 enhances allergen responsiveness

Pruritus is a common symptom of inflammatory skin conditions, including atopic dermatitis (AD). Although primary sensory neurons that transmit pruritic signals are well-cataloged, little is known about the neuronal alterations that occur as a result of skin disruption in AD. To address this question, we examined the molecular and behavioral consequences of challenging Grhl3PAR2/+ mice, which overexpress PAR2 in suprabasal keratinocytes, with serial topical application of the environmental allergen house dust mite (HDM). We monitored behavior and used RNA sequencing, qPCR, and in situ hybridization to evaluate gene expression in trigeminal ganglia (TG), before and after HDM. We found that neither Grhl3PAR2/+ nor wild-type (WT) mice exhibited spontaneous scratching, and pruritogen-induced acute scratching did not differ. In contrast, HDM exacerbated scratching in Grhl3PAR2/+ mice. Despite the absence of scratching in untreated Grhl3PAR2/+ mice, several TG genes in these mice were up-regulated compared to WT. HDM treatment of the Grhl3PAR2/+ mice enhanced up-regulation of this set of genes and induced additional genes, many within the subset of TG neurons that express TRPV1. The same set of genes was up-regulated in HDM-treated Grhl3PAR2/+ mice that did not scratch, but at lesser magnitude. Finally, we recorded comparable transcriptional changes in IL31Tg mice, demonstrating that a common genetic program is induced in two AD models. Taken together, we conclude that transcriptional changes that occur in primary sensory neurons in dermatitis-susceptible animals underlie a genetic priming that not only sensitizes the animal to chronic allergens but also contributes to pruritus in atopic skin disease.

What is in your pantry? Entomologic anaphylaxis

Background: The booklouse, Liposcelis bostrychophila, is a potent environmental allergen clinically associated with rhinoconjunctivitis and asthma. Despite its known infestation of grain products, anaphylaxis from ingestion of this organism has, to our knowledge, not been previously reported. We present the case of a 44-year-old woman who developed anaphylaxis to ingested oats and rice shown to be contaminated with L. bostrychophila. Objective: The objective was to isolate a distinct antigen from L. bostrychophila implicated in a case of unexplained anaphylaxis. Methods: In vitro studies were obtained for relevant ingested materials and aeroallergens. Skin-prick testing (SPT) was performed with standard extracts, contaminated oats, fresh oats, and crushed L. bostrychophila. Western blots were conducted using subject and control serum to detect specific immunoglobulin E (IgE) against the grains and L. bostrychophila extract. Competitive inhibition immunoblotting was used to assess specificity of IgE binding. Results: In vitro studies and SPT were notable for positive responses to dust mite and flour contaminated by L. bostrychophila, along with contaminated oats. Testing results for fresh oat and rice were negative. Immunoblots that used the subject's serum revealed a strongly positive band in the contaminated oat and rice extracts at 24 kD, whereas dust-mite extract yielded a single 14-kD band. Isolated L. bostrychophila extract also yielded a 24-kD band. Competitive inhibition experiments demonstrated that the 24-kD band in the contaminated oat extract was immunologically distinct from the 14-kD dust-mite band. Conclusion: Our case highlights the importance of considering L. bostrychophila as a potential culprit for unexplained anaphylaxis due to ingested grain products. Given the ubiquitous presence of this insect, we suspect that this may be a more common problem than previously recognized.

Rush sublingual immunotherapy in canine atopic dermatitis: a prospective pilot study

Twenty dogs with canine atopic dermatitis (CAD) were treated with rush sublingual immunotherapy (SLIT), with a 48 hour build-up phase and 6 months maintenance phase (treated by antigen once every 3-4 weeks). The canine atopic dermatitis extent and severity index (CADESI)-4 was evaluated before treatment (baseline) and after 6 months. An open, non-controlled, non-randomized pilot trial was conducted to assess the effectiveness and safety of rush SLIT for environmental allergen extracts (Dematophagoides pteronyssinus and D.farinae mix and other). Three dogs dropped out and 17 dogs finished the trial. CADESI-4 at baseline was 60.6±27.1 (range 17-107, n=17). After 6 months of SLIT treatment, CADESI-4 was 37.4±36.0 (range 5-152, n=17) (p <0.01), which was a 38.3% reduction. A significant improvement, defined as a CADESI-4 reduction of > 30%, was observed in 13 out of 17 dogs (76%). A moderate improvement, defined as a CADESI-4 reduction of ≦30%, was observed in 2 dogs (12%). In the other 2 dogs (12%), CADESI-4 worsened or showed no change. However, no severe adverse effects were observed during the trial. Therefore, rush SLIT against environmental allergen extract for CAD showed effectiveness and safety as evidenced by the reduction of CADESI-4 after 6 months SLIT without severe adverse effects.