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Article Summaries - April 2014


(Parrish DW, Sharma S, Kumar S. Ann Allergy Asthma Immunol 2014; 112: 286-289)

  • Eosinophilic esophagitis (EoE): (i) pathogenesis: immune reaction to food or respiratory allergens in the esophagus → infiltration of eosinophils into esophageal mucosa (usually patchy) → chronic eosinophilic inflammation → esophageal dysfunction; (ii) common causal foods in children: milk, egg, soy, wheat, beef, chicken; (iii) common causal foods in adults: legumes, nuts, fruits, wheat, milk, soy, egg; (iv) frequent association with respiratory and skin allergies; (v) often misdiagnosed as GERD.
  • Diagnosis of EoE: (i) clinical history: abdominal pain, vomiting, dysphagia, food impaction, heartburn, cough, choking, food aversion, failure to thrive; (ii) esophageal endoscopy: white exudative plaques, mucosal rings (‘trachealization’), strictures, linear furrows, edema; (iii) esophageal biopsy (positive result: ≥15 eosinophils per high-power field; limitation: 5 biopsies represent only <0.02% of the esophageal surface → false negative results can occur, especially in mild cases); (iv) allergy testing (SPT, in vitro sIgE detection, patch test) with food and respiratory allergens; (v) food elimination-reintroduction trials; (vi) detection of eosinophil-mediated inflammation (e.g. cationic eosinophil granule proteins) by SPECT imaging
  • Treatment of EoE: (i) diet options: 6-food elimination diet (milk, egg, wheat, soy, fish/seafood, peanut/tree nuts), diet guided by allergy tests, aminoacid formula, (ii) corticosteroids (most recommended regimen: to swallow viscous budesonide respules mixed into a slurry-type solution with a sucralose-containing artificial sweetener); (iii) biologic therapies targeting the eosinophil (e.g. anti-IL-5 mAb, anti-IL-5R mAb).
  • Authors report the case of a 2-yr-old boy (author’s son) with EoE and intolerance to the sucralose-containing artificial sweetener (present in both the viscous budesonide preparation and the milk formula; the family helped a lot to get the correct diagnosis) → successful treatment: utilization of powdered sugar [viscous budesonide + 2 tsp of powdered sugar] and an unflavored aminoacid-based formula.
  • Author’s commentaries: (i) the consistency (thick enough to coat the esophagus), rather than the mixing ingredient, is likely the most important aspect of the steroid mixture for EoE treatment; (ii) it is essential to find a mixing food that the child tolerates (e.g. powdered sugar, honey, pancake syrup, pureed meal); (iii) parents’ ideas must be considered by the physicians.


(Uermösi C, Zabel F, Manolova V, Bauer M, Beerli RR, Senti G, Kündig TM, Saudan P, Bachmann MF. Allergy 2014; 69: 338–347):

  • Immune tolerance: nonresponsiveness of the adaptive immune system or active Treg cell response to antigens; mechanisms: Treg generation, anergy/deletion of reactive lymphocytes.
  • Immune tolerance is essential to prevent: (i) self-destruction; (ii) inflammatory response to beneficial or harmless exogenous molecules (e.g. food, commensal bacteria, allergens).
  • Loss of immune tolerance → allergic or autoimmune disorders (e.g. exposure to allergens in genetically susceptible subjects → specific TH2 responses → IgE-mediated allergies).
  • ~30% of the population in industrialized countries suffers from IgE-mediated allergies.
  • Allergen immunotherapy (AIT): (i) only therapy that has proved to provide long-term benefit and modulation of allergic disease; (ii) has been widely used to treat asthma, allergic rhinitis and venom allergy; (iii) promising therapy for atopic dermatitis and food allergy; (iv) it is necessary to improve AIT efficacy, safety and convenience.
  • How to ↑ efficacy and safety of AIT? (i) adding omalizumab (anti-IgE mAb); (ii) adding adjuvants (e.g. aluminum salts to slower allergen release from the injection site); (iii) using modified allergens (e.g. allergoids [altered allergens using formaldyde or glutaraldehyde to ↓ allergenicity while preserving immunogenicity], recombinant hypoallergenic allergens, tolerogenic peptides, recombinant DNA vaccines, allergens on virus-like particles), (iv) adding immune response modifiers (monophosphoryl lipid A [TLR-4 agonist], CpG-containing DNA [TLR-9 agonist], TLR8 agonists, probiotics, bacterial lysates, virus-like particles); (v) using other administration routes (epicutaneous, intralymphatic, intradermal, intranasal, oral); (vi) personalizing AIT schemes; (vii) inhibiting IgE-mediated cell activation by engaging the inhibitory receptor FcγRIIB (Fcγ-Fcε fusion molecules; allergen-Fcγ fusion molecules).
  • Allergen-specific IgG can inhibit IgE-mediated mast cell degranulation by 3 mechanisms: (i) allergen-neutralization (blocking antibodies); (ii) engagement of the inhibitory FcγRIIB → coaggregation of FcγRIIB and FcεRI by IgG and IgE antibodies simultaneously bound to allergen → recruitment of phosphatase SHIP-1 → inhibition of FcεRI-mediated signaling; (iii) engagement of the inhibitory FcγRIIB → ↑ internalization of specific IgE/FcεRI → down-regulation of FcεRI-bound IgE (novel mechanism in mice, reported in the current article).
  • Author’s commentary: IgE replacement on mast cells occurs slowly → a rapid IgG-dependent elimination of IgE from the cell surface may allow long-term desensitization of mast cells.


(Mir SAV, Schady D, Olive AP, Nagy-Szakal D, Kellermayer R. Pediatr Allergy Immunol 2014: 25: 94–95)

  • Primary eosinophilic gastrointestinal disorders (EGID): eosinophilic esophagitis (EoE), eosinophilic gastroenteritis, eosinophilic colitis, eosinophilic proctitis.
  • Other diseases that can cause mucosal eosinophilia: inflammatory bowel disease, irritable bowel syndrome, celiac disease.
  • Mast cell–eosinophil interaction: (i) mast cell-derived IL-13 can recruit eosinophils; (ii) mucosal mast cells can be increased in adults and children with EoE.
  • Authors studied biopsies from 12 children with EGID (excluding EoE; average age=10.4 yrs) and 14 healthy controls (average age=12.3 yrs) → (i) there was a significant positive correlation between eosinophil and mast cell counts in control samples; (ii) there was no correlation between eosinophil and mast cell counts in EGID patients (disrupted mast cell–eosinophil interaction?); (iii) study limitation: the utilized staining only detects granulated mast cells (increased degranulated mast cells in EGID patients might have not been detected).


(Della Torre E, Mattoo H, Mahajan VS, Carruthers M, Pillai S, Stone JH. Allergy 2014; 69: 269–272)

  • IgG4: (i) 5% of total IgG; (ii) antiinflammatory properties (negligible binding to C1q; exchangeable heavy chains [“Fab arm exchange”] that prevents cross-linking of antigen; higher affinity toward inhibitory FcγRIIb than to activatory FcγRIIa and FcγRIIIa).
  • IgG4 autoantibodies are pathogenic in some autoimmune disorders (e.g. pemphigus vulgaris: IgG4 to desmoglein; idiopathic membranous glomerulonephritis: IgG4 to PLA-2 receptor).
  • IgG4-related disease (RD): (i) multi-organ fibroinflammatory disease (tumefactive lesions rich in T cells and IgG4-positive plasma cells); (ii) unclear pathogenesis (TH2 cells may have a pathogenic role); (iii) can affect almost every organ; (iv) usually affects middle-aged to elderly men; (v) common clinical manifestations: autoimmune pancreatitis, sialadenitis, orbital disease (typically affecting lacrimal gland), allergic diseases, eosinophilia, ↑ serum IgE; (vi) 30% of patients have normal serum IgG4 concentrations; (vii) histology: diffuse lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, storiform fibrosis, obliterative phlebitis, ↑ eosinophils; (viii) treatment: corticosteroids, immunosuppressants, rituximab.
  • Authors evaluated the prevalence of atopy, peripheral blood eosinophilia (PBE) and ↑ IgE in 70 patients (24–82 yrs old) with biopsy-proven IgG4-RD → (i) 43 patients (61%) had ↑ serum IgG4 levels; (ii) 22 patients (31%) were atopic (similar prevalence of atopy to the US general population); (iii) ~20% of nonatopic subjects had PBE and ↑ IgE (hypothesis: processes inherent to IgG4-RD itself may contribute to PBE and ↑ IgE); (iv) there was a positive correlation between serum IgG4 levels and both serum IgE and eosinophil counts.