Murat Türk

Combination of omalizumab and bee venom immunotherapy: does it work?

Bee venom immunotherapy (b-VIT) can be combined with omalizumab therapy in order to suppress systemic reactions developing due to b-VIT itself. Omalizumab acts as a premedication and gains time for the immunotherapy to develop its immunomodulatory effects. However, the combination of omalizumab and b-VIT is not always effective enough. Herein we present a patient in whom successful immunotherapy cannot be achieved with combination of omalizumab to b-VIT.

Comment on: “Targeting the PGD2/CRTH2/DP1 Signaling Pathway in Asthma and Allergic Disease: Current Status and Future Perspectives”

We read with great interest the report of Kupczyk and Kuna [1], in which they outline the PGD2/CRTH2/DP1 signaling pathway and its role in asthma/allergic disorders, and preclinical evidence indicating that blocking prostaglandin D2 (PGD2) signaling via receptor antagonists may offer a therapeutic benefit. We especially want to thank the authors for their comprehensive work. They report the results of 13 key clinical studies on molecules targeting the PGD2/CRTH2/DP1 signaling pathway in asthma and allergic diseases. The patients in these studies have either allergic rhinitis or atopic, eosinophilic asthma. However, studies on chronic rhinosinusitis with nasal polyposis (CRSwNP), aspirin-exacerbated respiratory diseases (AERD) and eosinophilic asthma with CRSwNP phenotypes are needed. We believe that these drugs may be more effective in patients with AERD. AERD is a distinct clinical syndrome characterized by chronic eosinophilic inflammation of the upper and lower airways with symptoms that are exacerbated by aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) [2]. This group, previously called Samter’s triad or aspirin intolerant asthma, was named AERD by Stevenson et al. [3]. In time, upper and lower airway symptoms were found to be related to not only aspirin, but also all cyclooxygenase (COX)-1 inhibitors in AERD patients [3, 4]. It is estimated that only approximately 10% of patients with nasal polyps and approximately 9% of patients with chronic rhinosinusitis have AERD [5]. In contrast, only approximately 7–10% of patients with asthma have AERD [4]. The prevalence of AERD can increase to approximately 15% among patients with severe asthma and a significant association between severe asthma and enhanced sinonasal inflammation has been reported [4, 6]. In AERD pathogenesis, the arachidonic acid pathway produces increased amounts of leucotrienes LTC4, LTD4 and LTE, which result in bronchoconstriction, airway mucus production and eosinophil migration. PGD2 levels, responsible for bronchoconstriction and eosinophil chemotaxis, also increase. Conversely, levels of PGE2— which lowers 5-lipoxygenase (5-LO) activity, leucotriene production and eosinophil migration—decrease [7]. Compared with aspirin-tolerant asthma, patients with AERD have higher eosinophil levels both in tissue and in blood, as well as increased tissue mast cell levels. Due to prostaglandin E2 receptor (EP2) deficiency, PGE2-mediated blockage of the 5-LO pathway occurs to a lesser extent, ensuring already high levels of leucotriene. When COX-1 is inhibited by NSAIDs (in the absence of COX-2), the production of PGE2, the anti-inflammatory prostanoid, decreases even more and together with PGD2 derived from mast cells, leucotriene production from eosinophils, mast cells and other cells increase dramatically [8–10]. Also, as thromboxane A2 (TxA2) decreases, LTC4 synthetase upregulates, resulting in more leucotriene production [7]. This letter refers to the original article available at doi:10.1007/ s40265-017-0777-2.

Last station in the eosinophilic asthma with chronic rhinosinusitis and/or nasal polyposis march: Eosinophilic asthma with radiological findings associated with blood eosinophilia

ABSTRACT Objective: Eosinophilic asthma with chronic rhinosinusitis and/or nasal polyposis (EA-CRS/NP) is a subphenotype of adult-onset eosinophilic asthma. Blood eosinophil levels are shown to be highly elevated in patients with EA-CRS/NP and have potential for tissue infiltration. We aimed to demonstrate the clinical features of the patients who have a blood eosinophil level above 10% and have thorax computed tomography findings due to blood eosinophilia. Methods: Patients who were followed up in our clinic between 2012 and 2017 were retrospectively evaluated. Inclusion criteria were as follows: 1) Eosinophilic severe asthma, 2) eosinophilia >10%, 3) chronic sinusitis and/or nasal polyps, 4) patients with pathologic findings on thorax computed tomography, 5) regular follow-up for at least 1 year. Results: We identified 36 patients who met the above criteria. We defined this group as “Eosinophilic Asthma with chronic Rhinosinusitis and/or nasal polyposis with Radiological findings related to blood eosinophilia” (EARR). The mean age was 44.9 ± 11 years and 64% were females. Nasal polyps, aspirin exacerbated respiratory disease, and atopy, were present in 81%, 47%, and 25% of the patients, respectively. The mean blood eosinophil count was 1828.6 cells/mm3 (19%). The majority of EARR patients had upper lobe dominant ground-glass opacities. The mean follow-up period was 3.2 ± 2.5 years. EARR patients did not evolve into eosinophilic granulomatous polyangiitis in the follow-up. Conclusions: This phenotype is the first eosinophilic asthma sub-phenotype reported in the literature. EARR is the final stage of the allergic march of EA-CRS/NP.

Ranitidine-Induced Anaphylaxis in a Patient with Acute COPD Exacerbation

Ranitidine is a well-tolerated H2-receptor antagonist commonly used in peptic ulcer treatment and stress ulcer prophylaxis. Anaphylaxis is rarely observed with ranitidine. We report the case of a patient who developed anaphylaxis after intravenous injection of ranitidine for acute COPD exacerbation. This article underlines the importance of awareness that in COPD acute exacerbation treatment, ranitidine, which is usually administered with methylprednisolone, also has anaphylaxis potential.

Is nonhomogeneous expression of tissue mast cells or allergen specific IgEs bound to tissue mast cells possible

Skin prick tests (SPTs) are widely used to demonstrate an IgE-mediated hypersensitivity reaction to a specific allergen. However, local allergic conditions cannot be diagnosed with SPTs. Local specific IgE production was only presented before in mucosal tissues. We present a patient with house dust mite sensitization that had variable SPTs results in different body regions.