Search

Chronic urticaria is a common and debilitating mast cell-driven skin disease presenting with itchy wheals, angio-oedema, or both. Chronic urticaria is classified as spontaneous (without definite triggers) and inducible (with definite and subtype-specific triggers; eg, cold or pressure). Current management guidelines recommend step-up administration of second-generation H1-antihistamines to four-fold the approved dose, followed by omalizumab and ciclosporin. However, in many patients, chronic urticaria does not respond to this linear approach due to heterogeneous underlying mechanisms. A personalised endotype-based approach is emerging based on the identification of autoantibodies and other drivers of urticaria pathogenesis. Over the past decade, clinical trials have presented promising options for targeted treatment of chronic urticaria with the potential for disease modification, including Bruton's tyrosine kinase inhibitors, anti-cytokine therapies, and mast cell depletion. This Therapeutics article focuses on the evidence for these novel drugs and their role in addressing an unmet need for personalised management of patients with chronic urticaria.

Many patients with chronic spontaneous urticaria (CSU) do not achieve complete control of their symptoms with current available treatments. In a dose-finding phase 2b study, ligelizumab improved urticaria symptoms in patients with H1-antihistamine (H1-AH) refractory CSU. Here, we report the efficacy and safety outcomes from two ligelizumab phase 3 studies.

Urticaria, the second most common drug eruption after exanthematous drug eruptions, (1) is characterized by episodic short-lived swellings of the skin, oropharnyx, or genitalia. Transient leakage of plasma from small [...]

Chronic spontaneous urticaria (CSU) can present with non–skin related symptoms (NSRS), including recurrent unexplained fever, joint, bone, or muscle pain (JBMP), and malaise, which also occur in other conditions that manifest with wheals (eg, urticarial vasculitis or autoinflammatory disorders) or without wheals (eg, infection).

Mastocytosis is a neoplasm characterized by an accumulation of mast cells in various organs and increased risk for severe anaphylaxis in patients with concomitant allergies. Coronavirus disease 2019 (COVID-19) is a pandemic that is associated with a relatively high rate of severe lung disease and mortality. The mortality is particularly high in those with certain comorbidities and increases with age. Recently, several companies have developed an effective vaccination against COVID-19. Although the reported frequency of severe side effects is low, there is an emerging discussion about the safety of COVID-19 vaccination in patients with severe allergies and mastocytosis. However, even in these patients, severe adverse reactions are rare. We therefore recommend the broad use of COVID-19 vaccination in patients with mastocytosis on a global basis. The only well-established exception is a known or suspected allergy against a constituent of the vaccine. Safety measures, including premedication and postvaccination observation, should be considered in all patients with mastocytosis, depending on the individual personal risk and overall situation in each case. The current article provides a summary of published data, observations, and expert opinion that form the basis of these recommendations.

Hereditary alpha-tryptasemia (HAT) is a genetic trait caused by an increased alpha-tryptase tryptase alpha/beta 1gene copy number.Basal serum mast cell tryptase (MCT) level is typically greater than or equal to 8.0 ng/mL.

Background:Indolent systemic mastocytosis (ISM) is a rare, clonal haematological neoplasm driven by the KITD816V mutation in up to 95% of cases. It is characterized by a debilitating, heterogenous and unpredictable symptom burden due to mast cell mediator release among patients. Treatment is limited to symptom management with no approved targeted therapies in the UK. The Indolent Systemic Mastocytosis Symptom Assessment Form (ISM-SAF ©) (Taylor et al.[2021]) is a validated symptom-assessment tool developed specifically for ISM patients focusing on 11 symptoms over a 24-hour recall period: bone pain, abdominal pain, nausea, skin spots, itch, flushing, fatigue, dizziness, brain fog, headache and diarrhoea. Each symptom is scored on a scale from 0-10. To date, there has not been any published UK data examining symptom burden in ISM patients. Subsequently we assessed symptom burden utilising the ISM-SAF © in our patient cohort at Guy's and St Thomas' Hospital.

Introduction

Patients with chronic spontaneous urticaria (CSU) have spontaneous wheals (W), angioedema (AE), or both, for longer than 6 weeks. Clinical differences between patients with standalone W, standalone AE, and W and AE (W+AE) remain incompletely understood.

There are substantial knowledge gaps related to diagnosis and management of pediatric cases of chronic urticaria, and in particular chronic spontaneous urticaria (CSU). In this article we aimed to review the diagnosis and management of chronic urticaria in children and CSU in particular. We conducted a systematic review of articles published in English and French on pediatric CSU management in the last 10 years. We included experimental studies (eg, randomized controlled trials), other experimental designs (eg, nonrandomized methods of assignment, controlled before-after studies, and interrupted time series), and observational studies (eg, prospective or retrospective cohort studies, cross-sectional studies, case-control studies, and case reports). Our findings highlight the efficacy of second-generation antihistamines for the treatment of CSU in children and supports the use of omalizumab for more severe cases. However, our study also reveals severe knowledge gaps related to the best management strategy in children with more severe/refractory cases of CSU. Future studies are required to establish the beneficial effect of high doses of second-generation antihistamines as well as the effectiveness and safety of omalizumab and other biologics in young children.

Indolent systemic mastocytosis, including the subvariant of smouldering systemic mastocytosis, is a lifelong condition associated with reduced quality of life. Masitinib inhibits KIT and LYN kinases that are involved in indolent systemic mastocytosis pathogenesis. We aimed to assess safety and efficacy of masitinib versus placebo in severely symptomatic patients who were unresponsive to optimal symptomatic treatments.

Chronic spontaneous urticaria (CSU) is a distressing disease. We report real-world data from the global Chronic Urticaria Registry (CURE) about associations between various CSU states and sleep impairment, plus important health-related quality-of-life (HRQoL) outcomes and compared different methods to assess CSU states.

In 2002, the European Competence Network on Mastocytosis (ECNM) was launched as a multidisciplinary collaborative initiative to increase the awareness and to improve diagnosis and management of patients with mast cell disorders. The ECNM consists of a net of specialized centers, expert physicians and scientists who dedicate their work to mast cell diseases. One essential aim of the ECNM is to timely distribute all available information about the disease to patients, doctors, and scientists. In the past 20 years, the ECNM has expanded substantially and contributed successfully to the development of new diagnostic concepts, the classification, prognostication, and treatments of patients with mastocytosis and mast cell activation disorders. The ECNM also organized Annual Meetings and several Working Conferences supporting the development of the WHO classification between 2002 and 2022. In addition, the ECNM has established a robust and rapidly expanding patient registry and has supported the development of new prognostic scoring systems and new treatment approaches. In all projects, ECNM representatives collaborated closely with their US colleagues, various patient organizations, and with other scientific networks. Finally, ECNM members have started several fruitful collaborations with industrial partners, leading to the preclinical development and clinical testing of KIT-targeting drugs in systemic mastocytosis, and some of these drugs received licensing approval in recent years. All these networking activities and collaborations have strengthened the ECNM and supported our efforts to increase awareness of mast cell disorders and to improve diagnosis, prognostication and therapy in patients.

The present article reviews childhood urticaria. It provides an update on the current understanding of its pathophysiology and highlights the current practice in the management of this condition.

Urticaria is characterised by transient swellings of the skin, which fluctuate over hours. Deeper swellings of the subcutaneous and submucosal tissue are known as angio-oedema. Drug-induced urticaria has been reported with a wide range of drugs and vaccines. NSAIDs and antibiotics are the drugs most commonly associated with urticaria, although reliable data from prospectively controlled studies is scarce. Spontaneous reports of drug-induced urticaria to the Committee on Safety of Medicines, UK, over a 40-year period also implicate bupropion, selective serotonin re-uptake inhibitor antidepressants, angiotensin-converting enzyme inhibitors (ACEI), H2 and H1 antihistamines, and systemic antifungals. New evidence suggests that selective COX-2 inhibitors may be tolerated in patients with aspirin-sensitive urticaria. The safety of angiotensin II receptor antagonists in patients with angio-oedema induced by ACEI has not yet been established.

Background: Circulating autoantibodies against FcϵRI, IgE, or both occur in approximately one third of patients with chronic idiopathic urticaria (CIU), but not all autoantibodies initiate histamine release. Objective: We sought to classify patients with CIU into subsets on the basis of serum bioactivity and immunoreactivity and to examine the relationship between newly defined subtype and disease severity. Methods: Sera from patients with CIU (n = 78), dermog-raphism (n = 15), and cholinergic urticaria (n = 10) and sera from healthy subjects (n = 39) were analyzed by means of Western blot analysis for anti-FcϵRI autoantibodies and for histamine release from basophils and dermal mast cells. In vivo reactivity of autologous serum was tested by means of intradermal injection, and CIU severity was determined on the basis of clinical interview. Results: We classified sera from patients with CIU into 5 subsets: immunoreactive histamine-releasing anti-FcϵRI autoantibodies (n = 20 [26%]); immunoreactive anti-FcϵRI autoantibodies without histamine-releasing activity (n = 12 [15%]); anti-IgE-like autoantibodies (n = 7 [9%]); serum containing a mast cell-specific histamine-releasing factor (n = 7 [9%]); and sera with no identifiable factor (n = 32 [41%]). Patients with serum histamine-releasing activity had more severe urticaria than patients without such activity. Positive skin test responses to autologous sera were associated with histamine-releasing anti-FcϵRI autoantibodies but not with non-histamine-releasing anti-FcϵRI autoantibodies. Neither healthy subjects nor patients with dermographism or cholinergic urticaria had his-tamine-releasing anti-FcϵRI autoantibodies. Conclusion: These data support the specificity of functional anti-FcϵRI autoantibodies to CIU. The identification of distinctive subsets of patients suggests that other pathogenic mechanisms occur in CIU in addition to direct ligation of FcϵRI by autoantibodies causing dermal mast cell degranulation. Elucidating these mechanisms might lead to new treatments for CIU. (J Allergy Clin Immunol 2002;110:492-9.)

Chronic urticaria has a spectrum of clinical presentations and causes. About 50% of patients with “idiopathic” disease have histamine-releasing autoantibodies in their blood. The term autoimmune urticariais increasingly being accepted for this subgroup of patients, in whom immunosuppressive therapies may be appropriate if conventional approaches to management are unsuccessful. This article reviews the classification, causes, and management of chronic urticaria in light of recent advances in the understanding of its etiology. (J Am Acad Dermatol 2002;46:645-57.) Learning objective:At the conclusion of this learning activity, participants should have up-to-date knowledge of the classification, assessment, and management of chronic urticaria and understand where the concept of autoimmune urticaria fits into existing frameworks.

Cross: Novartis: Consultancy, Research Funding; Incyte: Consultancy. McLornan:Jazz Pharmaceuticals: Honoraria, Speakers Bureau; Novartis: Honoraria. Radia:Blueprint Medicines: Consultancy; Novartis: Consultancy, Speakers Bureau.There are very few medications available in mastocytosis and various off label medications have been used including pegylated interferon alpha.

For the prevention of attacks of hereditary angioedema (HAE), the efficacy and safety of subcutaneous human C1-esterase inhibitor (C1-INH[SC]; HAEGARDA, CSL Behring) was established in the 16-week Clinical Study for Optimal Management of Preventing Angioedema with Low-Volume Subcutaneous C1-Inhibitor Replacement Therapy (COMPACT).

Data from the 3 omalizumab pivotal trials in patients with chronic idiopathic urticaria/chronic spontaneous urticaria (CIU/CSU) represent the largest database of patients reported to date with refractory disease (omalizumab, n = 733; placebo, n = 242).

Systemic mastocytosis(SM) is diagnosed when clonal, neoplastic mast cells are demonstrated in extracutaneous tissues. SM is a heterogeneous disorder ranging from indolent disease to aggressive multisystem involvement. We have an established mastocytosis working group in our Trust which was registered with the European Competence Network of Mastocytosis(ECNM) in 2005. We present data prospectively collected using an ECNM algorithm for the management of SM patients over 5 years.120 cases of cutaneous mastocytosis have been discussed at 3 monthly multidisciplinary meetings with dermatology colleagues. Full blood counts, liver, bone profile and DEXA scans are reviewed with clinical symptoms and treatments. Patients with a tryptase level of >20ng/ml are offered haematology review and bone marrow investigation. In addition patients referred directly to haematology for a second opinion have their cases and bone marrows reviewed. Bone marrow samples are sent for c-kit D816V mutation analysis.Classification of SM patients. 59/120 (46%) patients were offered bone marrow biopsies. Tryptase levels for these ranged from 15.1–760ng/ml (median 51.5ng/ml).4 patients declined biopsy.5/55 had normal biopsies and were c-kit negative.50 patients had SM.47/50(94%) met the WHO major criteria and 3/50(6%) minor criteria. These were subclassified-38/50(76%) had Indolent Systemic Mastocytosis(ISM);1/50 (2%) had Smouldering Systemic Mastocytosis(SSM);5/50(10%) had Aggressive Systemic Mastocytosis and 6/50(12%) had Systemic Mastocytosis with associated haematologiocal non-mast cell lineage disorder(SM-AHNMD). The bone marrow trephine disease burden was variable:ASM (range 5–100%), SSM 20%, ISM (5-45%) and AHNMD (5-100%). Tryptase levels reflected total disease bulk including cutaneous burden. C-KIT D816V mutation 44 patients with SM had samples analysed for the D816V mutation. 35 were positive (80%) and 9 negative (20%). Clinical Symptoms: 11/59 (19%) patients were asymptomatic (10 had ISM and 1 SSM).36/59 (61%) patients had urticarial symptoms needing symptomatic treatment (2 normal marrow, 2 AHNMD, 2 ASM and 30 ISM).16/59 (27%) patients had allergic symptoms ranging from mild allergies to anaphylaxis.(3 normal marrows, 13 ISM).13/59(22%) had gastrointestinal symptoms ranging from loose motions to severe colitis(1 normal marrow,1 ASM and 11 ISM). DEXA results:36/59(61%) patients had reported DEXA scans at our Trust, the rest reviewed locally. 6/36 (16%) had osteoporosis and required treatment. One 63yr old female patient has SM-AHNMD(MPD). 5 patients had ISM. 3 were females (age range 45–65yrs; tryptase levels 42.9, 49.1 and 60.5ng/ml)) and 2 male (both 45yrs: tryptase levels 31.2 and 47.8ng/ml). After 1 year of treatment with bisphophonates one of the male patients showed an improvement in his osteoporosis indices.7/36(19%) had osteopaenia reported all with a diagnosis of ISM.5 were male and 2 female (tryptase range 21.1–174ng/ml:median 40.3ng/ml).23/36(64%) patients had normal DEXA scans.Treatment regimes in patients with SM are for symptom control. Antihistamines, anti-inflammatory agents, anti-leucotriene agents, mast cells stabilising agents, bisphosphonates and steroids are used. In severe anaphylactic patients self administration of adrenaline is taught. Patients with ASM have been treated with various modalities e.g. Cladrabine, Alpha Interferon, Dasatinib, Imatinib (D816V negative patients) and Midostaurine with variable partial responses.2 patients with ASM have died due to rapidly progressive disease.2 AHNMD patients have an associated MPD (1 Jak 2 postive) and are being treated with pegylated alpha interferon and venesection.2 AHNMD patients died as a result progressive acute myeloid leukaemia and Non Hodgkins Lymphoma.2 AHNMD patients (MDS/MGUS) are being monitored.Our data reflects the heterogeneous nature of this disorder both clinically and in the histological classification. Patients with ISM can have severe clinical manifestations and treatment needs to be tailored to the individual's symptoms. Assessment and surveillence for osteoporosis is vital for all patients. ASM patients have limited treatment options with variable and unsustained responses. Further development of evidence based novel therapies requires multicentred trials in this rare group of patients.Harrison: Incyte: Honoraria; Novartis: Honoraria.