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Article Summaries - July 2014


(Rodríguez-Sánchez J, Gómez Torrijos E, López Viedma B, de la Santa Belda E, Martín Dávila F, García Rodríguez C, Feo Brito F, Olmedo Camacho J, Reales Figueroa P, Molina-Infante J. Allergy 2014; 69: 936–942):

  • Eosinophilic esophagitis (EoE): (i) prevalence in the general population: ~1/2,000 subjects; (ii) incidence is rising; (iii) male to female ratio=3:1; (iv) impact: significant morbidity, ↓ QoL, high cost; (v) pathogenesis: genetic susceptibility, environmental insults to the esophageal epithelium (e.g. allergens, infections, irritants) → epithelial barrier dysfunction (e.g. ↓ expression of the cell adhesion protein DSG-1), ↑ secretion of TSLP and IL-33 → ↑ allergen entry through the epithelium → immune reaction to food or respiratory allergens → infiltration of eosinophils into esophageal mucosa → chronic inflammatory infiltrate (eosinophils, mast cells, a special basophil population, TH2 cells, iNKT cells) → esophageal fibrosis, remodelling (e.g. transdifferentiation of epithelial cells to a myofibroblast phenotype) and dysfunction; (vi) common causal foods in children: milk, egg, soy, wheat, beef, chicken; (vii) common causal foods in adults: legumes, nuts, fruits, wheat, milk, soy, egg; (viii) frequent association (40-90%) with other atopic diseases (asthma, allergic rhinitis, food allergy, atopic dermatitis).
  • Diagnosis of EoE: (i) clinical history: abdominal pain, vomiting, dysphagia, heartburn, cough, choking, food aversion; (ii) complications: food impaction, failure to thrive, esophageal perforation, mental affectation; (iii) esophageal endoscopy: edema, white exudative plaques, mucosal rings (‘trachealization’), strictures, linear furrows, mucosal tearing; (iv) esophageal biopsy (positive result: ≥15 eosinophils per high-power field; other findings: superficial layering, microabscesses, extracellular eosinophil granules, basal cell hyperplasia, dilated intercellular spaces, lamina propria fibrosis); (v) allergy testing (skin prick test [SPT], serum specific IgE, atopy patch test [APT]) with food and respiratory allergens; (vi) food elimination-reintroduction trials; (vii) 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) topical corticosteroids: low bioavailability and low potential for systemic adverse effects but ↑ risk of local fungal infection; (iii) systemic corticosteroids: effective, severe side effects; (iv) biologic therapies targeting the eosinophil (e.g. anti-IL-5 mAb, anti-IL-5R mAb); (v) esophageal dilation: might provide short-term symptomatic relief, only used if dietary and medical therapy has failed.
  • Efficacy of dietary therapies in EoE: (i) elemental diet (in both children and adults): ~90%; (ii) empiric 6-food elimination diet (SFED) (in both children and adults): ~70%; (iii) diet guided by skin testing (SPT and atopy patch test): ~75% in children, ~30% in adults.
  • Authors compared the efficacy of food-specific serum IgE-targeted elimination diet (sIgE-ED) and SFED in 43 adults with EoE → (i) mean number of eliminated foods per patient was significantly lower in sIgE-ED (3.81) than in SFED (6); (ii) most commonly foods withdrawn by sIgE-ED: wheat (85%), nuts (73%), cow’s milk (61%); (iii) sIgE-ED was effective, comparable to SFED in terms of clinical and histological remission; (iv) causative foods identified by food challenge: cow’s milk (64%), wheat (28%), egg (21%), legumes (7%); (v) serum specific IgE was more accurate than SPT and APT to detect offending foods (sensitivity 87.5%, specificity 68%), especially for cow´s milk.


(Furuta GT, Atkins FD, Lee NA, Lee JJ. Ann Allergy Asthma Immunol 2014; 113: 3-8):

  • Dynamic history of eosinophils (4 eras since Paul Erlich named them based on eosin staining): (i) Paul Erlich to the Mid-20th Century (1880-1960): eosinophils are innate defense cells (destruction of large nonphagocytable parasites) and causal agents of allergic diseases and tissue damage; (ii) The Early Anti-inflammatory Years (1960-1980): eosinophils are recruited to inflamed tissues to ↓ the inflammatory activity of resident leukocytes (e.g. mastocytes); (iii) The “Gleich Era” (1980-2000): rebirth of the nonspecific and destructive nature of eosinophils contributing to host defense and diseases (enzymatic and cytotoxic activity of granule proteins); (iv) The LIAR Hypothesis (2000-present): eosinophils contribute to tissue homeostasis through local immune and remodeling/repair activities (e.g. liver and skeletal muscle regeneration)
  • Eosinophil functions: (i) proinflammatory: cytotoxicity, tissue damage, angiogenesis; (ii) antiinflammatory: tissue repair and remodeling, immunomodulation.
  • Diseases with ↑ eosinophils: (i) allergic diseases (atopic dermatitis, asthma, allergic rhinitis); (ii) hypereosinophilic syndrome; (iii) eosinophilic organ diseases; (iv) eosinophilic vasculitis (Churg-Strauss syndrome); (v) eosinophilic leukemia; (vi) other inflammatory processes.
  • Eosinophilic activity in disease: (i) measurement methods: blood or tissue eosinophil counts, levels of eosinophil proteins in tissues or fluids; (ii) ↓ eosinophilic activity is usually associated with disease remission; (iii) to date, no eosinophil-related biomarker has proved sufficient utility as a surrogate of disease symptomatology, natural history, outcome or therapeutic success.
  • Specific therapies targeting the eosinophil: (i) molecules: anti-IL-5 mAbs (mepolizumab, reslizumab), anti-IL-5Rá mAb (benralizumab, which also depletes basophils); (ii) variable efficacy in studies of patients with asthma, eosinophilic GI diseases, atopic dermatitis, Churg-Strauss syndrome and FIP1L1/PDGFRA-negative HES (outcomes appear to depend on the patient phenotype and/or primary end point examined); (iii) more research is necessary.
  • Additional therapeutic targets to ↓ eosinophils: eotaxins, CCR3, CRTH2 (Chemoattractant Receptor-homologous molecule expressed on TH2 cells), TH2-associated cytokines.
  • Absence of eosinophils in mice or humans → no significant deleterious effect on health (apparently).


(Jagdis A, Vadas P. Ann Allergy Asthma Immunol 2014; 113: 115-116):

  • Monoclonal mast cell activation syndrome (MMAS): (i) 1st described in 2007; (ii) definition: clonal mast cell disorder characterized by recurrent symptoms of mast cell degranulation (urticaria, bronchospasm, abdominal symptoms, hypotension) in patients who do not fulfill criteria for systemic mastocytosis (SM); (iii) patients with MMAS meet only 1 or 2 of the minor criteria for SM and do not exhibit the clusters of bone marrow mast cells; (iv) unknown natural history (some patients eventually fulfill the 3 minor criteria for SM); (v) therapy: antihistamines, antileukotrienes, mast cell stabilizers, corticosteroids; (vi) disease control can be difficult.
  • Omalizumab: (i) recombinant humanized anti-IgE mAb → binds to free IgE → ↓ IgE binding to its receptors, ↓ expression of IgE receptors → ↓ IgE-mediated inflammation; (ii) FDA-approved for severe asthma and antihistamine-refractory CU; (iii) efficacy has also been reported in mast cell activation disorders, anaphylaxis, eosinophilic chronic rhinosinusitis and atopic dermatitis.
  • Authors report the case of a 31-yr-old woman with recurrent unprovoked life-threatening anaphylaxis (urticaria, swelling, cough, dyspnea, chest tightness, dysphonia, abdominal pain, vomiting, hypotension, syncope, marked ↑ of serum tryptase) → laboratory: normal CBC,  minimal ↑ of baseline serum tryptase, IgE=68 IU/mL → bone marrow biopsy: mild ↑ of mast cells and eosinophils, one compact cluster of mast cells (not meeting major criterion for SM), occasional mast cells with spindled morphology, rare mast cells with weak anti-CD25 staining → cytogenetic analysis: Asp816Val c-KIT mutation → diagnosis: MMAS →  unsuccessful therapy: cetirizine (20 mg/d), ranitidine (150 mg bid), sodium cromoglycate (200 mg tid), montelukast (10 mg/d), ketotifen (4 mg bid), desloratadine (5 mg/d), hydroxychloroquine (200 mg/d) → partially successful therapy: omalizumab 300 mg SC every 4 wks continuously → follow-up at 11 months: 1 anaphylactic reaction requiring epinephrine, 2 milder reactions, no adverse effects of omalizumab, ↓ use of ketotifen (3 mg bid) and montelukast (suspended).
  • Author’s commentaries: (i) 3rd reported case of omalizumab efficacy in MMAS (unclear mechanism of action); (ii) omalizumab may help patients with life-threatening refractory MMAS.