Martin K Church

Institute for Allergology Charité Universitätsmedizin Berlin

Niniejsza aktualizacja i rewizja międzynarodowych wytycznych dotyczących pokrzywki została opracowana zgodnie z metodami zalecanymi przez Cochrane i grupę roboczą Grading of Recommendations Assessment, Development and Evaluation (GRADE). Jest to wspólna inicjatywa Dermatology Section of the European Academy of Allergology and Clinical Immunology (E...

Chronic urticaria (CU) is a mast cell (MC)‐dependent disease with limited therapeutic options. Current management strategies are directed at inhibiting IgE‐mediated activation of MCs and antagonizing effects of released mediators. Due to the complexity and heterogeneity of CU and other MC diseases and mechanisms of MC activation—including multiple...

Background: Patients with chronic spontaneous urticaria (CSU) have spontaneous wheals, angioedema, or both for >6 weeks. Clinical differences between patients with standalone wheals (W), standalone angioedema (AE), and wheals and angioedema (W+AE) remain incompletely understood. Objective: To compare W, AE, and W+AE CSU patients regarding demogr...

Background: allergic rhinoconjunctivitis and chronic urticaria are common histamine-driven diseases, exerting detrimental effects on cognitive functions, sleep, daily activities and quality of life. Non-sedating second-generation H1-antihistamines are the first line treatment of choice. Aim of the study was to define the role of bilastine among se...

Background Guidelines recommend standard doses of antihistamines as first-line, and updosing of antihistamines as second-line treatment for the management of chronic urticaria (CU). However, remission rates with different types of first- and second-line treatments and indicators of antihistamine response are largely lacking in the literature. Obje...

Background Chronic inducible urticaria (CIndU) constitutes a group of nine different CIndUs in which pruritic wheals and/or angioedema occur after exposure to specific and definite triggers. Histamine released from activated and degranulating skin mast cells is held to play a key role in the pathogenesis of CIndU, but evidence to support this has,...

Chronic urticaria (CU) is a mast cell-driven chronic inflammatory disease with a female predominance. Since CU affects mostly females in reproductive age, pregnancy is an important aspect to consider in the context of this disease. Sex hormones affect mast cell (MC) biology, and the hormonal changes that come with pregnancy can modulate the course...

Background Chronic prurigo (CPG) is characterized by intensive itch and nerve-neuropeptide-mast cell interactions. The role of some neuropeptides such as cortistatin and its receptor MRGPRX2 in CPG is poorly investigated. Objectives We evaluated (i) whether cortistatin activates human skin mast cells (hsMCs), and (ii) whether cortistatin and MRGPR...

Cutaneous mast cells are central to urticaria pathogenesis and histamine is the major mediator of swelling and itch. Other cells in lesional skin biopsies of chronic spontaneous urticaria include T cells, eosinophils, basophils and neutrophils. The role of these cells and their interactions is not yet clear during wheal development and resolution....

This update and revision of the international guideline for urticaria was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI),...

Background Although well described in adults, there are scarce and heterogeneous data on the diagnosis and management of chronic urticaria (CU) in children (0–18 years) throughout Europe. Our aim was to explore country differences and identify the extent to which the EAACI/GA²LEN/EDF/WAO guideline recommendations for pediatric urticaria are impleme...

H1 receptor antagonists, known as H1-antihistamines (AHs), inactivate the histamine H1-receptor thereby preventing histamine causing the primary symptoms of allergic diseases, such as atopic dermatitis, pollinosis, food allergies, and urticaria. AHs, which are classified into first-generation (fgAHs) and second-generation (sgAHs) antihistamines, ar...

H1-antihistamines have been the mainstay of urticaria treatment since their introduction almost 80 years ago. For discussion they may be classified into first generation and second generation H1-antihistamines. The use of first generation H1-antihistamines should be discouraged in clinical practice today for two main reasons. First, they are less e...

Background: Although well described in adults, there are scarce and heterogeneous data on the diagnosis and management of chronic urticaria (CU) in children (0-18 years) throughout Europe. Our aim was to explore country differences and identify the extent to which the EAACI/GA²LEN/EDF/WAO guideline recommendations for paediatric urticaria are imple...

Background Cholinergic urticaria (CholU) is characterized by the occurrence of itchy wheals induced by sweating. Intradermal injections of acetylcholine (ACh) have been proposed to help with diagnosing CholU and subgrouping of patients, but controlled studies are largely missing. Objective To compare the rates of positive ACh test results in well...

Objective Immunoglobulin E (IgE) and its receptor, FcɛRI, importantly contribute to the pathophysiology of chronic spontaneous urticaria (CSU). Recent findings point to a possible role of total IgE as a marker of CSU disease activity, endotypes, and responses to treatment. The evidence in support of total IgE included in the diagnostic workup of pa...

The current therapeutic algorithm for chronic spontaneous urticaria (CSU), endorsed by the international guideline, entails treatment escalation from second‐generation H1‐antihistamines (sgAHs) to omalizumab and cyclosporine until complete response is achieved. Recently, several predictors of response to these treatment options have been described....

Histamine has long been known to be an inflammatory mediator in allergic and associated diseases. Following their discovery in the 1930s, H1-antihistamines were first introduced into clinical practice in the 1940s. Since that time three further histamine receptors, H2, H3 and H4, have been discovered and drugs to prevent their effects introduced. H...

Chronic urticaria (CU) is defined by the recurrence of wheals and/or angioedema for more than 6 weeks. It is divided into chronic inducible urticarias (CIndU) and chronic spontaneous urticaria (CSU), previously termed chronic idiopathic urticaria. In CIndU, signs and symptoms are provoked by a specific and definite trigger such as exercise, frictio...

Background IgG autoantibodies against the high‐affinity IgE receptor, FcɛRIα, contribute the pathogenesis of autoimmune chronic spontaneous urticaria (CSU). However, it is not known whether such patients also exhibit IgM or IgA autoantibodies against FcɛRIα. To address this question we developed an ELISA to assess serum levels of IgG, IgM, and IgA...

Background Chronic spontaneous urticaria (CSU) is considered an autoimmune disorder in 50% of cases at least, in which T and mast cell mediators are considered to be the primary cause of symptoms. However, H1‐antihistamines, cyclosporine A and omalizumab fail to achieve complete symptom amelioration in up to 70% of patients. This suggests that othe...

Chronic spontaneous urticaria (CSU) is considered to be primarily a mast cell-driven disease. However, recent evidence suggests that eosinophils may also have an axial role in symptomology. Histological studies have demonstrated the presence of both eosinophils and eosinophil granules, indicative of activation, in CSU lesions. While many allergic a...

Hereditary autoinflammatory diseases are caused by gene mutations of the innate immune pathway, e.g. nucleotide receptor protein 3 (NLRP3). Here, we report a four-generation family with cold-induced urticarial rash, arthralgia, chills, headache and malaise associated with an autosomal-dominant inheritance. Genetic studies identify a substitution mu...

This paper is to draw attention to the problems CU patient with angioedema encounter in countries with limited financial resources. Omalizumab is a valuable therapeutic option in such cases but the access to it is restricted due to its high price.

Objective: Bilastine is a potent and highly selective H1-antihistamine approved for the treatment of allergic rhinoconjunctivitis and urticaria. This article summarizes available data on the use of bilastine in the treatment of allergic disorders in different age groups, including younger and older adults, and school-age children and adolescents. M...

The symptoms of chronic urticaria, be it chronic spontaneous urticaria (CSU) or chronic inducible urticaria (CindU), are mediated primarily by the actions of histamine on H1‐receptors located on endothelial cells (the wheal) and on sensory nerves (neurogenic flare and pruritus). Thus, 2nd generation H1‐antihistamines (sgAHs) are the primary treatme...

Background and objective: Pruritus is a major symptom of many inflammatory diseases and impacts greatly the quality of life in patients. We aimed to specify the characteristics of experimentally induced pruritus in normal skin and in experimentally induced inflammatory dermatitis in healthy volunteers. Methods: Skin inflammation was induced by t...

Background: Chronic spontaneous urticaria (CSU) is characterized by the degranulation of skin mast cells and the influx of basophils and eosinophils to affected skin sites. Blood basopenia has been linked to severe antihistamine-resistant CSU and type IIb autoimmunity, whereas the role of eosinophils in CSU is largely unknown. Objective: We analyz...

Background Autoimmune chronic spontaneous urticaria (aiCSU) is an important subtype of chronic spontaneous urticaria (CSU) in which functional IgG autoantibodies to IgE or its high‐affinity receptor (FcεRI) induces mast cell degranulation and subsequent symptom development. However, it has not been tightly characterized. This study aimed to better...

Background: In skin diseases and experimental models of pruritus, pure itch is accompanied by additional sensations that are poorly characterized. Objectives: This study compared the sensory qualities evoked by different models of experimentally induced pruritus including skin prick testing (SPT) with histamine or capsaicin and application of co...

Abstract Skin microdialysis (SMD) is a versatile sampling technique that can be used to recover soluble endogenous and exogenous molecules from the extracellular compartment of human skin. Due to its minimally invasive character, SMD can be applied in both clinical and preclinical settings. Despite being available since the 1990s, the technique has...

Received: December 14, 2018 Accepted: December 17, 2018 Published online: March 26, 2019 Issue release date: May 2019

The necessary treatment duration of omalizumab in patients with severe asthma remains unclear. Currently, common practice is life-long therapy without adjustment of dose or treatment intervals. This study evaluated asthma control after either dosage interval extension or dose reduction in patients with asthma controlled by omalizumab. Thirty-seven...

Chronic spontaneous urticaria (CSU) is a skin disease related to autoreactive IgE in at least a subgroup of patients. However, the nature of this autoreactive IgE remains poorly characterized. This investigation had three objectives: first, to quantity CSU autoreactive IgE; second, to recognize the patterns of CSU autoreactive IgE compared with hea...

Purpose The necessary treatment duration of omalizumab in patients with severe asthma remains unclear. Currently, common practice is life-long therapy without adjustment of dose or treatment intervals. This study evaluated asthma control after either dosage interval extension or dose reduction in patients with asthma controlled by omalizumab. Meth...

Diese evidenz- und konsensbasierte Leitlinie wurde entsprechend den Methoden der Cochrane und der Grading of Recommendations Assessment, Development and Evaluation (GRADE)-Arbeitsgruppen entwickelt. Die Leitlinien-Konferenz fand am 1. Dezember 2016 statt. Sie ist eine gemeinsame Initiative der European Academy of Allergology and Clinical Immunology...

Histamine and its receptors (H1R–H4R) play a crucial and significant role in the development of various allergic diseases. Mast cells are multifunctional bone marrow-derived tissue-dwelling cells that are the major producer of histamine in the body. H1R are expressed in many cells, including mast cells, and are involved in Type 1 hypersensitivity r...

The study of autoimmunity mediated by immunoglobulin E (IgE) autoantibodies, which may be termed autoallergy, is in its infancy. It is now recognized that systemic lupus erythematosus, bullous pemphigoid (BP), and chronic urticaria, both spontaneous and inducible, are most likely to be mediated, at least in part, by IgE autoantibodies. The situatio...

This evidence and consensus-based guideline was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. The conference was held on December 1st, 2016. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinica...

Background: The efficacy of omalizumab (anti-IgE) and elevated IgE levels in chronic spontaneous urticaria (CSU) suggest autoallergic mechanisms. Objective: To identify autoallergic targets of IgE in CSU patients. Methods: Sera of CSU patients together with idiopathic anaphylaxis patients and healthy controls (seven of each) were screened for...

Six years ago, we reviewed what was then known about chronic urticaria (CU) in children.¹ We came to the conclusion that many important and interesting questions were unanswered. These included, but were not limited to, how common chronic spontaneous urticaria (CSU) and inducible urticaria are in children, the clinical presentation, underlying caus...

Chronic urticaria (CU) is a group of common and debilitating conditions containing both chronic spontaneous urticaria (CSU) and chronic inducible urticarias (CIndU) including cold urticaria (ColdU) [1]. While antihistamines and omalizumab are effective treatments for both CSU and ColdU [2], many patients show insufficient response to either or both...

Introduction: HPMC-p, an inert micronized powder form of hydroxy-propyl-methyl-cellulose, when insufflated nasally, provides a natural barrier against pollen allergens and noxious agents. This overview assesses the efficacy and safety of this patented powder product and delivery system without an analogue among the cellulose derivatives. Areas Cove...

This review set out to examine published papers detailing the efficacy of bilastine in skin models and urticaria to assess whether it meets the optimal profile for updosing in urticaria, i.e. strong clinical efficacy and freedom from unwanted side effects, particularly sedation. Bilastine is a highly effective H1 -antihistamine even when used at th...

Opinion Statement Urticaria is primarily a disease driven by the actions of mast cell-derived histamine on the dermal vasculature and sensory nerves. Initial treatment with second generation minimally sedating H1-antihistamines is recommended. Start with the standard dose of one tablet daily. Because of the high local levels of histamine in the ski...

Chronic spontaneous urticaria (CSU) is a mast cell-driven disease that is defined as the recurrence of wheals, angioedema, or both for >6 weeks due to known or unknown causes. As of yet, disease diagnosis is purely clinical. Objective tools are needed to monitor the activity of CSU and the efficacy of treatment. Recently, several reports have sugge...

A slow response to omalizumab (anti-IgE) in CSU patients is strongly correlated with IgG-anti-FcεRI-mediated serum-induced basophil histamine release suggesting that, in these patients, effects on FcεRI are critical for the mechanism of action of omalizumab.

Chronic spontaneous urticaria (CSU) is a mast-cell driven skin disease, characterized by the recurrence of transient wheals, angioedema, or both for more than 6 weeks. Autoimmunity is thought to be one of the most frequent causes of CSU. Type I and type II autoimmunity, i.e. IgE to autoallergens and IgG autoantibodies to IgE or its receptor, respec...

Background: Schnitzler syndrome is an adult-onset autoinflammatory disease characterized by urticarial exanthema and monoclonal gammopathy accompanied by systemic symptoms such as fever, bone, and muscle pain. Up to now, approved treatment options are not available. Objective: We assessed effects of the anti-IL-1β mAb canakinumab on the clinical...

Allergic rhinitis results from an immunological abnormality in which atopic individuals produce immunoglobulin E (IgE) to allergens (e.g. pollen, house dust mites, animal dander and moulds). IgE activates mast cells, which respond by releasing inflammatory mediators. Histamine stimulates the early symptoms, predominately mucus production, nasal itc...

Background Atopic dermatitis (AD) is a common skin disorder. Its diagnosis relies on clinical judgment. Mild and untypical manifestations may cause diagnostic difficulties. Biomarkers for the differential diagnostic workup of AD are needed. Objective To test whether the results of skin provocation with cowhage, an established model of histamine-ind...

Understanding penetration not only in intact, but also in lesional skin with impaired skin barrier function is important, in order to explore the surplus value of nanoparticle-based drug delivery for anti-inflammatory dermatotherapy.

This supplement reports proceedings of the second international Global Urticaria Forum, which was held in Berlin, Germany in November 2015. In 2011, a report of the GA(2) LEN task force on urticaria outlined important and unanswered questions in chronic urticaria (CU). These included, but were not limited to, questions on the epidemiology and cours...

Background: Histamine intolerance and pseudoallergy to foods have been suggested to be causes of chronic spontaneous urticaria (CSU) with some patients reporting exacerbation with histamine-rich foods. Objective: The study aim was to identify the rate of histamine-intolerant CSU patients and to characterize the relevance of histamine intolerance...

Background: Cholinergic urticaria (CholU) is a frequent chronic urticaria disorder with itchy weal and flare-type skin reactions in response to physical exercise or passive warming. A higher frequency of atopy among CholU patients has been reported, but the significance of this observation is unclear. Objective: To assess the prevalence and rele...

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Background: Mastocytosis is a heterogeneous disease characterized by a clonal expansion of mast cells in various organs. The vast majority of patients affected suffer from signs and symptoms caused by mediator release from mast cells. Although the disease burden is high, there is currently no specific instrument to measure health-related quality o...

This chapter concentrates on the role in allergic disease of histamine acting on H1-receptors. It is clear that allergy has its roots in the primary parasite rejection response in which mast cell-derived histamine creates an immediate hostile environment and eosinophils are recruited for killing. This pattern is seen in allergic rhinitis where the...

Background: Tick bite-induced galactose-α-1,3-galactose (α-Gal) IgE and subsequent ingestion of red meat may cause delayed severe allergic reactions including urticaria, gastrointestinal symptoms or anaphylaxis. We tested the hypothesis that increased levels of IgE to α-Gal due to tick bites and the subsequent ingestion of red meat or meat product...

Interleukin-33 (IL-33) is a member of the interleukin-1 (IL-1) cytokine family. It is preferentially and constitutively expressed in different structural cells such as epithelial cells, endothelial cells, and smooth muscle cells. During necrosis of these cells (after tissue injury or cell damage), the IL-33 that is released may be recognized by dif...

The development of mature mast cells (MCs) from hematopoietic progenitor cells as well as the identification and characterization of committed progenitor cells are a current focus of mast cell research. Most published reports in this area are on the origin and differentiation of MCs in mice. Evidence for the human system, i.e. derived from primary...