urticaria

Cold urticaria is a condition characterized by wheals and/or angioedema in response to cold. It is usually diagnosed after provocation testing, and trigger thresholds measure its activity. Just as “common” urticaria, cold urticaria is also a mast-cell driven condition, where cold is an activating signal which causes a release of histamine from dermal mast cells. Cold agglutinins and cryoglobulins were designated as elements related to cold urticaria. The objective of this study was to understand the impact of cold agglutinins and cryoglobulins on the molecular level and evaluate strategies for cold urticaria.

This was a single-center prospective cohort study that included 35 participants with cold urticaria. They were analyzed for cold agglutinins and cryoglobulin, demographics, history data, cold stimulation test results, complete blood count values, C-reactive protein, total immunoglobulin E levels, and basal serum tryptase levels.

Sixteen (46%) of the 35 participants tested positive for cold agglutinin, and 9 (27%) of 33 tested participants had a positive cryoglobulin test. There was no gender association for cryoglobulin. However, a positive cold agglutinin was mainly in female participants. Also, a positive cold agglutinin test showed a higher rate of reactions triggered by cold ambient air, immersion in cold water, and aggravated by summer humidity. These participants also had more angioedema triggered by cold foods or drinks.

Cold agglutinin serum levels correlated with erythrocyte and monocyte counts. Cryoglobulin concentrations associated with basal serum tryptase levels and cold urticaria duration.

In conclusion, this study suggests that cold agglutinins and cryoglobulins are related to the course and pathogenesis of cold urticaria. More studies are encouraged to explore mechanisms of action, treatment, and use as biomarkers.

Urticaria is characterized by itchy wheals and/or angioedema. It is a common condition with an impact on the quality of life driven by mast cells. Numerous studies have demonstrated that serum levels of 25-hydroxyvitamin D can impact urticaria. However, the relation between vitamin D and urticaria is not well recognized. The objective of this study was to systematically synthesize the associations of vitamin D and urticaria published until March 2021.

A systematic search was done in PubMed, EMBASE, Web of Science, and Cochrane. Observational studies with the comparisons of vitamin D and people with urticaria and clinical studies were included.

A meta-analysis of 17 studies of urticaria patients compared to controls demonstrated a mean difference of -9.35 ng/mL in vitamin D, which complied with the association of urticaria with a deficiency in vitamin D. Studies with supplementation of vitamin D also demonstrated a significant reduction in clinical urticarial score in people supplemented with vitamin D.

In conclusion, people with urticaria may have a lower level of serum vitamin D, and vitamin D supplementation may reduce urticaria symptoms and exacerbations and improve quality of life due to vitamin D immunomodulatory and anti-inflammatory properties. However, more studies are needed to assess the clinical benefits and mechanisms of action of vitamin D in urticaria.

The causes of urticaria vary with patients, with hives mainly characterizing most of them. Urticaria can be classified as acute or chronic according to its duration. Most patients have triggers that cause exacerbations, which should be avoided to help control the disease. This review aims to describe the factors that may trigger chronic urticaria and angioedema, highlighting its mechanisms.

The major drug groups that may trigger urticaria include nonsteroidal anti-inflammatory drugs, antibiotics (especially beta-lactams), vaccines, bupropion, antidepressants, antihypertensives, H2 antihistamines, antifungals, and H1 antihistamines. Other drugs that decrease the degradation of bradykinin (from the mast cell degranulation cascade) lead to angioedema and include angiotensin-converting enzyme inhibitors, neutral endopeptidase, and dipeptidyl peptidase-4 inhibitors, resulting in the accumulation of bradykinin, followed by localized vasodilation and then angioedema.

Food and food components may also trigger urticaria or angioedema, such as food additives and naturally occurring substances (biogenic amines and aromatic compounds).

Other triggers of angioedema without urticaria include emotional distress, physical exertion, mechanical trauma, infection, menstruation, pregnancy, medical procedures, weather changes, alcohol ingestion, and some medicinal products.

In conclusion, patients with urticaria or angioedema must know trigger factors to introduce changes in their lifestyle and an individualized approach to treatment.

Chronic urticaria is an inflammatory condition characterized by wheals, angioedema, or both for more than six weeks. Women are more affected, and it is thought that sex hormones have a modulation capacity in women with urticaria. The objective of this study was to assess the evolution and characteristics of chronic urticaria during pregnancy.

PREG-CU was an international, multicenter study of the Urticaria Centers of Reference and Excellence (UCARE) network that included 288 women with chronic urticaria who became pregnant within the last three years and completed a 47-item questionnaire.

A total of 288 pregnancies of 288 women with chronic urticaria from 13 countries were analyzed. Half of the women reported their chronic urticaria had improved, 29% reported worsening, and 20% didn’t notice changes. Urticaria exacerbations happened mainly in the first or third trimester (22,8% and 27,6%, respectively). The risk factors were: mild disease and no angioedema before pregnancy, no treatment before pregnancy, exacerbation in a previous pregnancy, treatment during pregnancy, and stress. After giving birth, 44% of the women reported no changes in the disease, 37% reported worsening, and 18% improved.

In conclusion, pregnancy impacts the course of urticaria, and counsel and management should be done on a one-to-one basis. More prospective studies are needed to assess the importance and reliability of urticaria risk factors during pregnancy.

Urticaria is a skin disease characterized by rapid onset of hives (superficial dermis edema, erythema, pruritus, or burning sensation), which can be worsened by angioedema (edema of the deep dermis, fat tissue, and gastrointestinal tract). It reduces the quality of life of people and can consist of recurrent attacks. It can be considered acute urticaria or chronic urticaria if it takes longer than six weeks.

Chronic spontaneous urticaria is the most common and can be induced by autoreactivity or other causes. The diagnosis of chronic urticaria is usually complex and requires the exclusion of recurrent angioedema or hereditary angioedema, so biomarkers are essential to diagnose urticaria patients.

Currently, the assessment of chronic urticaria activity depends on the Urticaria Activity Score (UAS), with few evaluation indicators. Consistent biomarkers are needed to assess urticaria.

This article summarizes advanced biomarkers and related pathogenic pathways recently discovered, such as the cell adhesion/chemotaxis pathway, interleukin (IL)-6/Janus tyrosine kinase/STAT pathway, IL-17/IL-23 pathway, basophil- and mast cell-related pathway, coagulation/fibrinolysis-related pathways, single-nucleotide polymorphism, and some other pathways.

This review aims to discover adequate biomarkers to assess disease activity, find novel therapeutic targets, and predict the patients’ response to therapeutic agents (table 1).

Table 1. Biomarkers uses in urticaria

Chronic spontaneous urticaria (CSU) consists of wheals, angioedema, or both for longer than six weeks. Guidelines have limited procedures during the routine workup; however, some patients might need additional investigations. The objective of this article is to propose recommendations for the diagnostic and evaluation of some urticaria patients.

An extensive literature search was performed to identify important questions that should define diagnostic procedures based on expert consensus and published evidence.

The authors proposed seven questions for all chronic spontaneous urticaria patients: Confirm (rule out a differential diagnosis); Cause (look for indications of CSU); Cofactors (identify potential triggers, aggravators); Comorbidities (check for chronic inducible urticaria, autoimmunity, and mental health); Consequences (identify problems with sleep, distress, sexual health, work, and social performance); Components (assess potential biomarkers or predictors of treatment response); Course (monitor CSU activity, impact, and control).

Also, a complete medical history should be conducted in the assessment of the patient. CSU should be confirmed in all patients through a differential diagnosis, including blood testing for CRP and/or erythrocyte sedimentation rate and complete blood count with differential.

In conclusion, based on the answers, a decision for or against more diagnostic tests should be conducted by the specialist to prevent unnecessary and expensive testing and increase treatment effectiveness.

In chronic spontaneous urticaria, cutaneous mast cells are activated to initiate the process. There are different triggers, including the hypothesis that it is an autoimmune disease not driven by exposure to an exogenous agent.

It is characterized by a perivascular non-necrotizing cellular infiltrate around small venules of the skin. These infiltrates include CD4+ lymphocytes, Th2 and Th1 subtypes, Th17 cell-derived cytokines, neutrophils, eosinophils, basophils and monocytes, which contribute to the pathogenesis and responsiveness to steroid

This review focuses on each cell’s contribution to the inflammatory response and a view toward developing therapeutic options.

Immunohistochemistry can help reveal the function of each cell within the perivenular infiltrate. Rituximab efficacy is probably due to the prevention of autoantibody synthesis. Corticosteroids inhibit the function of T lymphocytes and eosinophils and prevent egress of most cell types from the bloodstream into tissues.

In the future, there may be studies that include drugs with increasing specificity in the course of urticaria, such as secukinumab (targets IL-17), dupilumab (targets TH-2 dependent cytokines, IL-4 and IL-3), mepolizumab, reslizumab and benralizumab (target TH2 and eosinophil-dependent cytokines), avdoralimab (complement C5a receptor) and lirentelimab (targets Siglec-8 on the surface of mast cells and eosinophils).

Chronic spontaneous urticaria impacts the quality of life and emotional well-being of people suffering from it. People with chronic spontaneous urticaria have increased emotional distress, anxiety, depression, somatoform disorders, and stress, which correlates with the activity of urticaria.

People with chronic spontaneous urticaria may be more susceptible to stressors and thus have increased stress responses. Stress responses may lead to the secretion of neuropeptides from sensory skin nerves, interacting with mast cells and releasing histamine, causing chronic spontaneous urticaria attacks.

This study compared the stress responses to acoustic startle and stress levels between 47 people with chronic spontaneous urticaria and 56 healthy volunteers. Stress levels were evaluated with the Perceived Stress Scale.

The stressor exposure session was three minutes long. Participants were exposed to 40 randomly spaced auditory startle stimuli. Responses to the stimuli were measured by electromyography assessment of the contraction amplitude of the orbicularis oculi muscle for each startle stimulus and the number of eye blinks.

People with chronic spontaneous urticaria had stronger responses to acoustic startles with high mean electromyography values and a higher number of eye blinks than healthy volunteers. People with urticaria also had longer stress responses and stress levels, as assessed by the Perceived Stress Scale.

In conclusion, people with urticaria have increased stress responses using objective and subjective measures. Underlying neuroimmune mechanisms should be studied further, as it is possible that stress predisposes to chronic spontaneous urticaria and that chronic spontaneous urticaria increases stress, forming a disease amplification loop.