Omalizumab, which is a monoclonal anti-IgE antibody, has recently been used as an option in the treatment of inducible urticaria.
We describe the case of a 46-year-old woman who was referred to the ...Department of Allergy and Immunology of "Hospital Civil de Guadalajara, Dr. Juan I. Menchaca" due to a history of hives, body itching, changes in the color of the skin after exposure to water, and chest tightness after the intake of cold beverages; therefore, she used to limit her outdoor activities and personal hygiene. We conducted challenge tests with heat, soaked towels, treadmill walks, and dermographism; which were negative. The ice cube test was positive. To establish the speed of wheal formation, we established intervals of exposure to cold of one, three, five, and ten minutes; a positive result was obtained from the third minute. Due to the poor response to the drug treatment and to measures to avoid the cold, as well as to the poor quality of life, the high risk of anaphylaxis, and the advent of winter season, omalizumab was administered at monthly doses of 150 mg during the winter season. After the first dose, there were no reports of episodes of hives in areas exposed to cold; the ice cube test was negative before the second dose and in the following months, and the patient was able to ingest cold beverages and cold food. There were no adverse reactions that could be attributable to the use of omalizumab. Three years after the first dose, the patient was still asymptomatic.
The described case is one of the first cases of cold urticaria with risk of anaphylaxis with a positive response to omalizumab, which was reflected in symptom control and the improvement in the quality of life.
Cold urticaria and your risk of anaphylaxis Belluco, Paulo Eduardo Silva; Sifuentes, Bárbara Garcia; Ferreira, Maurício Domingues
Revista Ciências em Saúde,
06/2021, Letnik:
11, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Cold urticaria (CU) is characterized by the appearance of wheals or angioedema after exposure to cold. It presents with mild to severe symptoms and can even lead to anaphylaxis. The risk of systemic ...reactions is high. We discuss this important pathology and show its strong relationship with anaphylaxis. Cold weather is one of the most common triggers for the onset of symptoms, with variables including humidity and thermal sensation. It is divided into acquired or familial forms. The diagnosis is made in patients with a medical history suggestive of the disease and should be confirmed with a stimulation test. The central aspect of treatment is to avoid cold stimuli. The prescription of self-injectable epinephrine for groups that are at high risk of systemic reactions is ideal. In conclusion, health professionals should be aware of CU in order to recognize the risk of anaphylaxis in these patients.
Cold Urticaria (ColdU) is a type of chronic inducible urticaria (CIndU) where recurrent pruritic wheals and/or angioedema occur after exposure to cold stimulus. Although it usually only affects ...exposed areas, systemic reactions can occur in severe cases. In this study, we seek to characterize the ColdU cases within our Centre's population of patients.
Retrospective study based on clinical files of patients diagnosed with ColdU followed in an urticaria outpatient clinic in Portugal prior to October 2020.
We included 52 patients total (40 women) with median age of 35 years, 19 patients with symptom onset before 18 years-old. ColdU was classified as acquired in all patients. Cold provocation tests were negative in 9 patients and these were classified as atypical ColdU. No significant differences were found between those with pediatric or adult onset of disease. Most of the patients had a localized form of the disease (52%). Despite not being statistically significant, it was found that patient's temperature threshold, assessed with TempTest® 4.0, was higher and stimulation time was shorter in more severe groups. All patients were treated with non-sedating antihistamines (daily or on-demand), finding that those controlled with standard dosages had lower temperature thresholds than those needing higher dosages (p < 0.01). One patient was under treatment with omalizumab.
ColdU is an heterogenous disease that can have life-threatening event consequences. Cold provocation tests and threshold assessment can be an important tool in the management treatment and in identifying severity groups.
This research letter provides guidelines for cold urticaria management established by the Centre of Evidence of Dermatology and the Urticaria Group of the French Society of Dermatology.
Cold urticaria (ColdU) is a common form of chronic inducible urticaria characterized by the development of wheals, angioedema or both in response to cold exposure. Recent research and guideline ...updates have advanced our understanding and management of ColdU. Today, its pathophysiology is thought to involve the cold‐induced formation of autoallergens and IgE to these autoallergens, which provoke a release of proinflammatory mediators from skin mast cells. The classification of ColdU includes typical and atypical subtypes. We know that cold‐induced wheals usually develop on rewarming and resolve within an hour and that anaphylaxis can occur. The diagnosis relies on the patient's history and cold stimulation testing. Additional diagnostic work‐up, including a search for underlying infections, should only be done if indicated by the patient's history. The management of ColdU includes cold avoidance, the regular use of nonsedating antihistamines and the off‐label use of omalizumab. However, many questions regarding ColdU remain unanswered. Here, we review what is known about ColdU, and we present important unanswered questions on the epidemiology, underlying pathomechanisms, clinical heterogeneity and treatment outcomes. Our aim is to guide future efforts that will close these knowledge gaps and advance the management of ColdU.
Background
Chronic inducible urticaria (CIndU) is characterized by mast cell (MC)‐mediated wheals in response to triggers: cold in cold urticaria (ColdU) and friction in symptomatic dermographism ...(SD). KIT receptor activation by stem cell factor (SCF) is essential for MC function. Barzolvolimab (CDX‐0159) is a humanized antibody that inhibits KIT activation by SCF and was well tolerated in healthy volunteers with dose‐dependent plasma tryptase suppression indicative of systemic mast cell ablation.
Methods
This is an open‐label, trial in patients with antihistamine refractory ColdU or SD, receiving one IV dose of barzolvolimab (3 mg/kg), with a 12‐week follow‐up. Primary endpoint was safety/tolerability; pharmacodynamic (PD)/clinical endpoints included serum tryptase, plasma SCF, skin MC histology, provocation tests, urticaria control test (UCT), and dermatology life quality index (DLQI).
Results
Analysis populations were safety (n = 21) and pharmacodynamics/clinical activity (n = 20). Barzolvolimab was well tolerated; most adverse events were mild and resolved. Treatment resulted in significant depletion of skin MCs, decreased tryptase (<limit of detection), and increased soluble SCF through Week 12. Complete responses (negative provocation test) occurred in 95% (n = 19/20) of patients (n = 10/10 ColdU; n = 9/10 SD), and all (n = 20/20) showed improvement in urticaria control (UCT ≥ 12). The kinetics of clinical activity mirrored that of MC and tryptase reduction. DLQI‐measured impairment significantly decreased to minimal/none in 93% of patients on study.
Conclusion
In CIndU patients, barzolvolimab was well tolerated, demonstrated marked, rapid, durable depletion of skin MCs, circulating tryptase, and reductions in clinical activity with significant improvements in disease control and quality of life (QoL) demonstrating potential therapeutic effects for MC‐mediated disorders.
In this Phase 1b study of CIndU (ColdU and SD) patients, barzolvolimab, a humanized antibody that inhibits KIT activation by SCF, was well tolerated. Barzolvolimab demonstrated marked, rapid, durable depletion of skin MCs, circulating tryptase, reductions in clinical activity, and significant improvements in disease control and QoL. Barzolvolimab has potential as a therapy for MC‐mediated diseases.Abbreviations: CIndU, chronic inducible urticaria; ColdU, cold urticaria; FcR, Fc receptor; Ig, immunoglobulin; KIT, KIT proto‐oncogene, receptor tyrosine kinase; MC, mast cell; MRGPRX2, mas‐related G protein‐coupled receptor‐X2; QoL, quality of life; SCF, stem cell factor; SD, symptomatic dermographism
Background
Cold urticaria (ColdU), that is, the occurrence of wheals or angioedema in response to cold exposure, is classified into typical and atypical forms. The diagnosis of typical ColdU relies ...on whealing in response to local cold stimulation testing (CST). It can also manifest with cold‐induced anaphylaxis (ColdA). We aimed to determine risk factors for ColdA in typical ColdU.
Methods
An international, cross‐sectional study COLD‐CE was carried out at 32 urticaria centers of reference and excellence (UCAREs). Detailed history was taken and CST with an ice cube and/or TempTest® performed. ColdA was defined as an acute cold‐induced involvement of the skin and/or visible mucosal tissue and at least one of: cardiovascular manifestations, difficulty breathing, or gastrointestinal symptoms.
Results
Of 551 ColdU patients, 75% (n = 412) had a positive CST and ColdA occurred in 37% (n = 151) of the latter. Cold‐induced generalized wheals, angioedema, acral swelling, oropharyngeal/laryngeal symptoms, and itch of earlobes were identified as signs/symptoms of severe disease. ColdA was most commonly provoked by complete cold water immersion and ColdA caused by cold air was more common in countries with a warmer climate. Ten percent (n = 40) of typical ColdU patients had a concomitant chronic spontaneous urticaria (CSU). They had a lower frequency of ColdA than those without CSU (4% vs. 39%, p = .003). We identified the following risk factors for cardiovascular manifestations: previous systemic reaction to a Hymenoptera sting, angioedema, oropharyngeal/laryngeal symptoms, and itchy earlobes.
Conclusion
ColdA is common in typical ColdU. High‐risk patients require education about their condition and how to use an adrenaline autoinjector.
The COLD‐CE study was carried out at 32 UCAREs from 19 countries and four continents. Among 551 ColdU patients, 75% had positive local CST (i.e., typical ColdU) and ColdA occurred in 37% of the latter. For the first time, we propose the criteria for adrenaline autoinjector prescription for patients with typical ColdU.Abbreviations: ColdA, cold‐induced anaphylaxis; COLD‐CE, comprehensive evaluation of cold urticaria and other cold‐induced reactions, a study of the GA2LEN UCARE network; ColdU, cold urticaria; CST, cold stimulation testing; UCAREs, Urticaria Centers of Reference and Excellence
Cold urticaria (CU) is an allergic reaction that manifests itself as hives-like rashes or red spots in response to general or local cooling of the body. Th e disease can be acquired or hereditary, ...and in the cold season it can affect all segments of the population. Th is pathological condition, at first glance, does not seem to be a very dangerous variant of a local cold injury, but in persons who are prone to exposure to low temperatures, especially with a burdened cold history, it may be accompanied by chronicity of the process and complicated by neurovasculitis, obliterating endarteritis and secondary Raynaud’s syndrome, may decrease the quality of life of the victims and become a cause of disability. The pathophysiology of CU is largely unknown, but it is likely to be related to immunoglobulin E (IgE) and mast cell activation. Cooling has been reported to induce the release of neutrophilic and eosinophilic chemotactic factors, prostaglandin D2, and tumor necrosis factor (TNF-α). Less common immunologic fi ndings in patients with CU include cryoglobulinemia consisting of monoclonal IgG and mixed IgG/IgM and IgG/IgA cryoglobulin types. The mechanisms of development of CU are mainly determined by the formation of cryoglobulins (cold hemolysins) and subsequent degranulation of mast cells. Th e diagnosis of CU depends on the patient’s history and the results of cold provocation tests. Patients with CU are recommended first of all not to overcool, to take warm showers, to wear warm clothes and a hat, and not to consume cold food and drinks. Treatment options include second-generation H1 antihistamines and glucocorticosteroids. New promising option is omalizumab, a humanized monoclonal antibody derived from a recombinant DNA molecule that targets and selectively binds to circulating IgE and affects mast cells function. In patients with CU undergoing general anesthesia, premedication including antihistamines and corticosteroids is recommended, along with strict maintenance of perioperative normotermia.
Холодова кропивниця (ХК) є алергічною реакцією, яка проявляється висипаннями за типом кропив’янки або червоних плям у відповідь на загальне або локальне охолодження тіла. Захворювання буває набутим або спадковим і в холодну пору року може уражувати всі верстви населення. Цей патологічний стан на перший погляд видається не дуже небезпечним варіантом локальної холодової травми, але в осіб, які схильні до впливу низьких температур, особливо з обтяженим холодовим анамнезом, може супроводжуватися хронізацією процесу й ускладнюватись нейроваскулітом, облітеруючим ендартеріїтом і вторинним синдромом Рейно, може знизити якість життя постраждалих і стати причиною інвалідності. Патофізіологія ХК мало вивчена, але ймовірно пов’язана з імуноглобуліном Е (IgE) та активацією тучних клітин. Охолодження тканин індукує викид хемотактичних факторів нейтрофілів та еозинофілів, простагландину D2 та фактора некрозу пухлин альфа (TNF-α). Менш частою імунологічною знахідкою у пацієнтів з ХК є кріоглобулінемія з моноклональними IgG та змішаними IgG/ IgM або IgG/IgA типами кріоглобулінів. Механізм розвитку ХК здебільшого визначається формуванням кріоглобулінів (холодних гемолізинів) та наступною дегрануляцією тучних клітин. Діагностика ХК залежить від анамнезу пацієнта та результатів холодових тестів. Пацієнтам з ХК рекомендують насамперед не переохолоджуватися, приймати теплий душ, носити теплий одяг та головний убір, не вживати холодну їжу та напої. Варіанти терапії включають H1-гістаміноблокатори другого покоління та глюкокортикоїди. Новою перспективною опцією є омалізумаб — моноклональне антитіло, яке отримують з рекомбінантної молекули ДНК і яке селективно зв’язує циркулюючий IgE і впливає на функцію тучних клітин. У пацієнтів з ХК, які підлягають загальній анестезії, в премедикацію рекомендовано включати антигістамінні та кортикостероїди, разом із суворим дотриманням періопераційної нормотермії.
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