Epidemiological and clinical characteristics of adult patients with chronic spontaneous urticaria in Latvia: insights from a two-centre study.

Chronic spontaneous urticaria (CSU) significantly impacts the quality of life of affected individuals. This study aimed to elucidate the epidemiological and clinical profiles of adult CSU patients in Latvia. Patient interviews and electronic medical records from two study centres in Riga, Latvia, were reviewed. PROMs, including UCT, UAS7, USS, and CU-Q2oL, were used to assess disease control, activity, severity, and quality of life. Statistical analysis was performed using Jamovi v. 2.3.28 and IBM SPSS v. 29.0.0.0. The cohort included 140 CSU patients (76.4% female; mean age 41.3 ± 14.9 years), mostly urban residents (87.1%) and non-smokers (53.6%). Urticaria with angioedema occurred in 52.1% and isolated urticaria in 47.9%, with 40% experiencing CSU for 1-5 years. Accompanying symptoms were reported by 63% and triggers by 72.9%. Allergy history and autoimmune disease diagnosis were noted in 49.3% and 29.3%. Treatment mainly involved second-generation antihistamines (85.7%) and omalizumab (17.9%). Mean scores for USS, UCT, and UAS7 were 28.8 (SD: 17.8), 8.2 (SD: 3.7), and 17.2 (SD: 14.1). UAS7 indicated severe CSU in 28.6%, and UCT suggested poorly controlled disease in 77.9%. CU-Q2oL total scores revealed mental status as the most affected domain (mean score: 51.7, SD: 28.7), with a significant association between accompanying symptoms and questionnaire scores. This study provides insights into the demographic and clinical aspects of CSU patients in Latvia, highlighting areas for potential improvement in patient care and emphasizing the need for further investigation into treatment outcomes and patient quality of life.

Assessment of clinical phenotypic characteristics of patients with angioedema without wheals in a turkish population.

Background: Angioedema (AE) is defined as localized, self-limited swelling of subcutaneous tissues and mucosa. Objective: The aim of this study was to compare the phenotypic characteristics of patients with AE without wheals. Methods: This prospective study included adult patients with recurrent AE without wheals. Demographic and laboratory data of the patients were recorded in the patient file when they presented to the outpatient clinic between August 2018 and August 2020. The patients were contacted by phone to evaluate whether their AE had gone into remission between October 2023 and January 2024. The phenotypic characteristics of AE subtypes were compared. Results: The study included a total of 143 patients. The average age, age of onset of AE, rates of diabetes mellitus, hypertension and coronary artery disease were higher in the patients with angiotensin-converting enzyme inhibitor (ACEI) use related acquired AE (AAE) (AAE-ACEI). The rates of allergic rhinitis, drug allergy, atopy, and aeroallergen sensitivity, and the median total immunoglobulin E level were higher in patients with idiopathic histaminergic AAE (AAE-IH). The rate of face and/or perioral AE attacks was higher in the patients with AAE-ACEI, AAE-IH, and idiopathic non-histaminergic AAE. The rate of AE attacks in limbs, abdominal, genital and other parts of the body was higher in patients with hereditary AE (HAE). The baseline AE activity score was lower in the patients with AAE-IH and higher in the patients with HAE. In long-term follow-up, the remission rate of AE attacks was significant higher in patients with AAE-ACEI and AAE-IH. Conclusion: The phenotypic characteristic features of Turkish patients with AE without wheals may vary, depending on the underlying AE pathogenesis. C1 inhibitor level and function, complement C4 and C1q, and genetic tests contributed to the diagnosis; other laboratory tests did not contribute to the diagnosis.

Chronic Inducible Urticaria.

Chronic inducible urticaria (CIndU) is characterized by the appearance of hives (urticaria) and/or angioedema in response to specific triggers or stimuli. For accurate diagnosis, anamnesis-driven specific, and if available, standardized trigger testings, as well as patient reported outcomes, should be applied. The currently recommended treatment algorithm is the same as for chronic spontaneous urticaria but is largely off-label for CIndU. New, and possibly more disease-specific, treatment options are needed for CIndU patients, who are often severely impacted by their disease. Several clinical trials are currently ongoing.

Classification, Diagnosis, and Pathology of Angioedema Without Hives.

A clear disease classification schema coupled with an understanding of the specific mechanisms involved in the different types of angioedema without hives informs the diagnostic assessment. The recommended approach involves several key steps. Foremost is the recognizing of the clinical clues which allow for the differentiation of mast cell-mediated disorders from bradykinin-mediated angioedema. Enhanced vascular permeability related to bradykinin is of critical importance to identify given the implications for disease morbidity and risk of mortality. The ability to efficiently categorize and diagnose all forms of angioedema results in improved patient outcomes.

Contact System Activation and Bradykinin Generation in Angioedema: Laboratory Assessment and Biomarker Utilization.

The role of contact system activation has been clearly established in the pathogenesis of hereditary angioedema due to C1 inhibitor deficiency (HAE-C1INH). C1 inhibitor (C1INH)-protease complexes, levels of functional C1INH, plasma kallikrein activation, and cleavage of high-molecular-weight kininogen have each been associated with disease activity. More recently, HAE with normal levels of C1INH (HAE-nl-C1INH) has been recognized. Six genetic mutations have been identified which are linked to HAE-nl-C1INH phenotypes. The majority of individuals with HAE-nl-C1INH fall into the unknown category. There is substantial evidence that bradykinin generation underlies the recurrent attacks of swelling in some of these cohorts.

Angioedema After Use of Recombinant Tissue-Type Plasminogen Activators in Stroke.

Angioedema without concomitant urticaria is a well-known complication of treatment with the recombinant tissue-type plasminogen activator (r-tPA) alteplase and its genetically modified variant tenecteplase. It is potentially lethal when causing airway obstruction and can require intubation. The latest guideline for the early management of patients with acute ischemic stroke from the American Heart Association/American Stroke Association advises to treat this complication initially by interfering with the histamine pathway. This article aims to clarify the pathophysiological mechanism of r-tPA-induced angioedema and provides several arguments that this condition is primarily bradykinin-mediated and hence should be treated initially by intervening with the bradykinin pathway. Second, other-less frequently reported-adverse symptoms after r-tPA therapy and their proposed pathophysiological mechanisms leading to specific treatment are described. This manuscript describes the need for an update of the section "3.5 IV alteplase" from the American Heart Association/American Stroke Association guideline to treat this r-tPA-induced angioedema adequately and prevent potentially fatal outcomes.

Analysis of coagulation factors in angioedema/urticaria: increased values of D-dimer and fibrinogen in isolated angioedema.

INTRODUCTION: Recent research has shown that blood coagulation and the extrinsic coagulation cascade are involved in the pathogenesis of chronic spontaneous urticaria (CSU), but little is known about the coagulation factors in angioedema. METHODS: This study included 58 participants: 29 patients with chronic angioedema (14 with isolated angioedema and 15 with angioedema with wheals) and 29 healthy controls (HCs). We compared the values of coagulation factors in patients with isolated angioedema to those with wheals. Plasma levels of D-dimer, fibrinogen, and factor VII were measured by enzyme-linked immunosorbent assay (ELISA) for all participants. RESULTS: Significantly higher D-dimer (p = 0.016; ε² = 0.381) and fibrinogen (p = 0.044; ε² = 0.331) levels were recorded in patients with angioedema (both groups) than in the HCs, with higher levels for angioedema with wheals. Factor VII and fibrinogen levels did not differ significantly between the groups with angioedema, but coagulation factors were more often elevated in both angioedema groups than in HCs. CONCLUSIONS: One characteristic of angioedema is an elevated blood coagulation potential, which may help produce fibrin and may be important in controlling angioedema attacks.

Update on Urticaria and Angioedema.

Urticaria and angioedema are caused by immunoglobulin E- and non-immunoglobulin E-mediated release of histamine and other inflammatory mediators from mast cells and basophils. Diagnosis is made clinically, and anaphylaxis must be ruled out if urticaria or angioedema is present. A limited nonspecific laboratory workup should be considered unless elements of the history or physical examination suggest specific underlying conditions. The mainstay of treatment is avoidance of triggers when and if triggers are identified. The first-line pharmacotherapy is second-generation H1 antihistamines, which can be titrated to greater than standard doses.

Mast cell degranulation and bradykinin-induced angioedema - searching for the missing link.

Initiation of the bradykinin generation cascade is responsible for the occurrence of attacks in some types of angioedema without wheals. Hereditary angioedema due to C1 inhibitor deficiency (HAE-C1-INH) is one such clinical entity. In this paper, we explore the existing evidence that mast cells (MCs) degranulation may contribute to the activation of the kallikrein-kinin system cascade, followed by bradykinin formation and angioedema. We present the multidirectional effects of MC-derived heparin and other polyanions on the major components of the kinin-kallikrein system, particularly on the factor XII activation. Although, bradykinin- and histamine-mediated symptoms are distinct clinical phenomena, they share some common features, such as some similar triggers and a predilection to occur at sites where mast cells reside, namely the skin and mucous membranes. In addition, recent observations indicate a high incidence of hypersensitivity reactions associated with MC degranulation in the HAE-C1-INH patient population. However, not all of these can be explained by IgE-dependent mechanisms. Mast cell-related G protein-coupled receptor-X2 (MRGPRX2), which has recently attracted scientific interest, may be involved in the activation of MCs through a different pathway. Therefore, we reviewed MRGPRX2 ligands that HAE-C1-INH patients may be exposed to in their daily lives and that may affect MCs degranulation. We also discussed the known inter- and intra-individual variability in the course of HAE-C1-INH in relation to factors responsible for possible variability in the strength of the response to MRGPRX2 receptor stimulation. The above issues raise several questions for future research. It is not known to what extent a prophylactic or therapeutic intervention targeting the pathways of one mechanism (mast cell degranulation) may affect the other (bradykinin production), or whether the number of mast cells at a specific body site and their reactivity to triggers such as pressure, allergens or MRGPRX2 agonists may influence the occurrence of HAE-C1-INH attacks at that site.

Definition, acronyms, nomenclature, and classification of angioedema (DANCE): AAAAI, ACAAI, ACARE, and APAAACI DANCE consensus.

BACKGROUND: Angioedema (AE) manifests with intermittent, localized, self-limiting swelling of the subcutaneous and/or submucosal tissue. AE is heterogeneous, can be hereditary or acquired, may occur only once or be recurrent, may exhibit wheals or not, and may be due to mast cell mediators, bradykinin, or other mechanisms. Several different taxonomic systems are currently used, making it difficult to compare the results of studies, develop multicenter collaboration, and harmonize AE treatment. OBJECTIVE: We developed a consensus on the definition, acronyms, nomenclature, and classification of AE (DANCE). METHODS: The initiative involved 91 experts from 35 countries and was endorsed by 53 scientific and medical societies, and patient organizations. A consensus was reached by online discussion and voting using the Delphi process over a period of 16 months (June 2021 to November 2022). RESULTS: The DANCE initiative resulted in an international consensus on the definition, classification, and terminology of AE. The new consensus classification features 5 types and endotypes of AE and a harmonized vocabulary of abbreviations/acronyms. CONCLUSION: The DANCE classification complements current clinical guidelines and expert consensus recommendations on the diagnostic assessment and treatment of AE. DANCE does not replace current clinical guidelines, and expert consensus algorithms and should not be misconstrued in a way that affects reimbursement of medicines prescribed by physicians using sound clinical judgment. We anticipate that this new AE taxonomy and nomenclature will harmonize and facilitate AE research and clinical studies, thereby improving patient care.

Subcutaneous panniculitis-like T-cell lymphoma: fever and facial swelling with hemophagocytic syndrome.

We report a case of subcutaneous panniculitis-like T-cell lymphoma (SPTCL) in a young man presenting with fever and facial swelling. He had pancytopenia and hemophagocytic syndrome (HPS) on evaluation. The histopathological examination of skin punch biopsy from the face and chest wall showed SPTCL. Given the associated HPS, he was started on steroid and multidrug chemotherapy following which he had symptomatic improvement.