[EFFECTS OF DUPILUMAB ON PERENNIAL ALLERGIC RHINITIS IN ATOPIC DERMATITIS PATIENTS].

BACKGROUND: Dupilumab, an anti-IL (Interleukin) -4 receptorα mAb, inhibits IL-4/IL-13 signaling and is indicated for the treatment of inadequately controlled AD, asthma and CRSwNP because IL-4/IL-13 signaling is a key driver of type2/Th2 immune diseases (atopic/allergic diseases). As well as the above diseases, a therapeutic effect of dupilumab on PAR can be expected. We investigated the effect of dupilumab on PAR in severe AD patients with comorbid PAR. METHODS: Prospective observational study. 21 severe AD patients with PAR who started dupilumab were enrolled and we devided them into 2 groups: more than moderate group and less than moderate group. We investigated subjective symptoms, QOL scores, face scale, findings of nasal cavity and laboratory findings before start of therapy and 12 months later. RESULTS: In more than moderate group, significant improvements were observed in subjective symptoms (except a part), QOL scores (except a part), face scale and findings of nasal cavity. On the other hand, in less than moderate group, no improvement was observed in all items. Subjective symptom assessments were estimated lowlier than objective finding assessments. CONCLUSION: Dupilumab has a therapeutic effect on severe PAR in severe AD patients.

Exploration of biomarkers to predict clinical improvement of atopic dermatitis in patients treated with dupilumab: A study protocol.

BACKGROUND: Atopic dermatitis (AD) is a common eczematous skin disorder that profoundly reduces the quality of life due to intractable pruritus. Excellent therapeutic success of the anti-interleukin 4 receptor-α antibody dupilumab in clinical trials and a real-world clinical context indicates the crucial roles of interleukin (IL)-4 and IL-13 in the pathogenesis of AD. Along with the clinical improvement in skin scores and pruritus, dupilumab significantly and progressively reduces and normalizes the upregulated expression of T helper type 2 signatures such as Chemokine (C-C motif) ligand (CCL)17, CCL18, CCL22, and CCL26 in the lesional skin of AD. However, no blood/serum biomarkers are known to predict good or poor outcome in patients with AD treated with dupilumab. METHODS: Patients are at least 18 years of age and have moderate-to-severe AD with Eczema Area and Severity Index (EASI) ≥16, Investigator's Global Assessment ≥3, and body surface area ≥10%. We are going to enroll more than 130 subjects from 18 medical facilities. Clinical objective findings will be evaluated by EASI. Subjective symptoms will be assessed by Patient-Oriented Eczema Measure, Numerical Rating Scale for Pruritus (Pruritus-NRS), Skin Comfort-NRS, and Treatment Satisfaction-NRS. We will measure 18 blood/serum biomarkers including % eosinophils in blood cell count, lactate dehydrogenase, total IgE, soluble interleukin 2 receptor, CCL17, CCL18, CCL22, CCL26, CCL27, IL-13, IL-22, IL-24, IL-25, IL-31, IL-33, thymic stromal lymphopoietin, periostin, and squamous cell carcinoma antigen-2. The clinical evaluation and biomarker sampling will be performed at 0, 2, 4, 8, and 16 weeks of dupilumab treatment. We will also perform proteomic analysis (of roughly 300 proteins) of the patients' sera obtained at 0 and 2 weeks of treatment. The primary endpoint is the association between "baseline levels of 18 biomarkers" and "% change from baseline of EASI at 16 weeks of dupilumab treatment." DISCUSSION: This is the first clinical trial to explore the biomarkers, including potential proteomic markers, most strongly associated with improvement in EASI in patients with moderate-to-severe AD treated with dupilumab for 16 weeks (B-PAD study). A limitation is that we will only enroll Japanese patients.

[A CASE OF FOOD-DEPENDENT EXERCISE-INDUCED ANAPHYLAXIS BY SHRIMP: FRUCTOSE 1, 6- BISPHOSPHATE ALDOLASE IS SUPPOSED AS CAUSATIVE COMPONENT DESPITE NEGATIVE ALLERGEN-SPECIFIC IGE TEST (IMMUNOCAP®)].

A 16-year-old male high-school student experienced generalized itchy wheal and dyspnea during physical exercise after lunch. Each food material of his lunch was examined using a prick-prick test, allergen-specific IgE test (ImmunoCAP®), and provocation test. The prick-prick test was positive for black tiger shrimp (raw and heated) and white leg shrimp (heated). Allergen-specific IgE test (ImmunoCAP®) showed absolutely negativity for all suspected foods. The food-exercise provocation test using heated black tiger shrimp with additional aspirin intake finally induced anaphylaxis.We studied the IgE-binding molecules from shrimp using a purification procedure and Western blotting, with sera from the patient and several controls. A 40-kDa protein, corresponding to FBA, was found to be the major IgE-binding allergen component in this patient. Currently, the precise history and the prick-prick test using both raw and heated shrimps are useful to diagnose shrimp-induced FDEIA. Because the allergen-specific IgE test is insufficient to diagnose the cause of the symptoms, a component allergen-specific IgE test after the identification of the causative allergenic protein, such as FBA, is required.