Cryoproteins, such as cryoglobulins, cryofibrinogens and cold agglutinins, precipitate at low temperatures or agglutinate erythrocytes and dissolve again when warmed. Their pathogenetic and ...diagnostic importance in cold urticaria (ColdU) is unclear. In this study, we aimed to characterize the prevalence of cryoproteins in patients with ColdU.
We conducted 3 analyses: i) a systematic review and meta-analysis of published data using an adapted version of the Joanna Briggs Institute's critical appraisal tool for case series, ii) a retrospective analysis of 293 ColdU patients treated at our Urticaria Center of Reference and Excellence (UCARE) from 2014 to 2019, and iii) a prospective observational study, from July 2019 to July 2020, with 49 ColdU patients as defined by the EAACI/GA2LEN/EDF/UNEV consensus recommendations.
Our systematic review identified 14 relevant studies with a total of 1151 ColdU patients. The meta-analyses showed that 3.0% (19/628), 1.1% (4/357) and 0.7% (2/283) of patients had elevated levels of cryoglobulins, cryofibrinogens and cold agglutinins, respectively. Our retrospective analyses showed that cryoproteins were assessed in 4.1% (12/293) of ColdU patients. None of 9 ColdU patients had cryoglobulins, and one of 5 had cold agglutinins. In our prospective study, none of our patients had detectable cryoglobulins (0/48) or cryofibrinogens (0/48), but 4.3% (2/46) of patients had cold agglutinins (without any known underlying autoimmune or hematological disorder).
Our investigation suggests that only very few ColdU patients exhibit cryoproteins and that the pathogenesis of ColdU is driven by other mechanisms, which remain to be identified and characterized in detail.
Background
Cold urticaria (coldU) is associated with substantial morbidity and risk of fatality. Data on coldU in children are sparse. We aimed to evaluate the clinical characteristics, management, ...risk of associated anaphylaxis, and resolution rate of coldU in a pediatric cohort. Additionally, we sought to compare these metrics to children with chronic spontaneous urticaria (CSU).
Methods
We prospectively enrolled children with coldU from 2013–2021 in a cohort study at the Montreal Children's Hospital and an affiliated allergy clinic. Data for comparison with participants with solely CSU were extracted from a previous study. Data on demographics, comorbidities, severity of presentation, management, and laboratory values were collected at study entry. Patients were contacted yearly to assess for resolution.
Results
Fifty‐two children with cold urticaria were recruited, 51.9% were female and the median age of symptom onset was 9.5 years. Most patients were managed with second‐generation H1‐antihistamines (sgAHs). Well‐controlled disease on sgAHs was negatively associated with concomitant CSU (adjusted odds ratio (aOR) = 0.69 95%CI: 0.53, 0.92). Elevated eosinophils were associated with cold‐induced anaphylaxis (coldA; aOR = 1.38 95%CI: 1.04, 1.83), which occurred in 17.3% of patients. The resolution rate of coldU was 4.8 per 100 patient‐years, which was lower than that of CSU (adjusted hazard ratio = 0.43 95%CI: 0.21, 0.89, p < 10−2).
Conclusion
Pediatric coldU bears a substantial risk of anaphylaxis and a low‐resolution rate. Absolute eosinophil count and co‐existing CSU may be useful predictive factors.
Cold Urticaria Syndromes: Diagnosis and Management Diaz, Vanessa L; Gribbons, K Bates; Yazdi-Nejad, Katayoun ...
The journal of allergy and clinical immunology in practice (Cambridge, MA),
08/2023, Letnik:
11, Številka:
8
Journal Article
Recenzirano
Cold urticaria is a chronic condition causing episodic symptoms of cold-induced wheals or angioedema in response to direct or indirect exposure to cold temperatures. Whereas symptoms of cold ...urticaria are typically benign and self-limiting, severe systemic anaphylactic reactions are possible. Acquired, atypical, and hereditary forms have been described, each with variable triggers, symptoms, and responses to therapy. Clinical testing, including response to cold stimulation, helps define disease subtypes. More recently, monogenic disorders characterized by atypical forms of cold urticaria have been described. Here, we review the different forms of cold-induced urticaria and related syndromes and propose a diagnostic algorithm to aid clinicians in making a timely diagnosis for the appropriate management of these patients.
Cold-induced urticaria is a kind of physical urticaria characterized by the appearance of wheals after exposure to cold. The atypical form is a rare sub-type characterized by appearance of hives even ...in areas not directly exposed to the cold and by a negative cold stimulation test. Its diagnosis is often challenging because of the lack of specific tests and it is usually based on the patient's clinical history. Hypotension due to generalized exposure to the cold is described both in the typical and the atypical forms.
We describe a 9-year-old boy who, at the beginning of the summer after the first swim in the sea, developed generalized urticaria, dyspnea, conjunctival hyperemia, blurred vision and loss of strength. The child was treated with intramuscular steroid and intravenous antihistamine, and the symptoms quickly resolved. Insect bite, contact with fish and drug ingestion were denied, and no unusual food had been eaten before the swim. A tentative diagnosis was made of either aquagenic urticaria or cold urticaria, but the specific tests were negative. Although the cause was unknown, prophylactic treatment with antihistamines was prescribed but in spite of this, wheals developed all over the body, after every swim in the sea. The child then came to our attention and relying on clinical history a diagnosis of atypical cold urticaria was made: development of hives even in areas not directly exposed to cold and a negative response to the cold stimulation test, are the characteristic features of this rare form of cold urticaria.
Atypical cold urticaria should be suspected in all cases of anaphylaxis related to cold exposure (i.e. contact with water) with a negative cold stimulation test.
Background
Cold urticaria (ColdU) is characterized by pruritic wheals following exposure of the skin to cold. Many patients show insufficient response to antihistamines, the first line treatment. ...Based on the high efficacy of interleukin‐1(IL‐1)‐inhibition in cold‐induced urticarial autoinflammatory diseases, we assessed the effects of rilonacept, an IL‐1 inhibitor, in ColdU patients unresponsive to standard treatment.
Methods
In this randomized, double‐blind, placebo‐controlled two‐center study, we included 20 patients with ColdU. In the first part, patients received 320 mg rilonacept or placebo (1:1) followed by weekly doses of 160 mg rilonacept or placebo for 6 weeks. In the second part, all patients received weekly 160 mg or 320 mg rilonacept for 6 weeks, open‐label. The primary endpoint was change in critical temperature threshold (CTT). Secondary endpoints included changes in quality of life impairment (Dermatology Life Quality Index, DLQI), differences of inflammatory mediators upon cold provocation and safety assessment over the study period.
Results
Baseline mean CTTs were 20.2°C (placebo) and 17.3°C (rilonacept). Mean CTTs did not change significantly during the 6‐week double‐blind treatment (placebo – 0.45°C; rilonacept +0.89°C). IL‐6, IL‐18 and HSP‐70 blood levels showed interindividual variability without significant changes during hand cold water bath provocation in placebo‐ or rilonacept‐treated patients. In contrast, DLQI significantly improved in the rilonacept (mean DLQI reduction of 3.8; p = 0.002) but not in the placebo group (mean DLQI reduction of 0). Comparing baseline with the rilonacept open‐label treatment, there were no changes in CTTs or DLQI scores.
Conclusion
IL‐1 inhibition with rilonacept did not improve ColdU, but demonstrated a good safety profile.
Clinical Trial Registration
EudraCT number: 2012‐005726‐30. ClinicalTrials.gov identifier: NCT02171416.
Background Data about special phenotypes, natural course, and prognostic variables of patients with acquired cold urticaria (ACU) are scarce. Objectives We sought to describe the clinical features ...and disease course of patients with ACU, with special attention paid to particular phenotypes, and to examine possible parameters that could predict the evolution of the disease. Methods This study was a retrospective chart review of 74 patients with ACU who visited a tertiary referral center of urticaria between 2005 and 2015. Results Fourteen patients (18.9%) presented with life-threatening reactions after cold exposure, and 21 (28.4%) showed negative results after cold stimulation tests (classified as atypical ACU). Nineteen patients (25.7%) achieved complete symptoms resolution at the end of the surveillance period and had no subsequent recurrences. Higher rates of atypical ACU along with a lower likelihood of achieving complete symptom resolution was observed in patients who had an onset of symptoms during childhood ( P < .05). In patients with atypical ACU, shorter disease duration and lower doses of antihistamines required for achieving disease control were detected ( P < .05). Age at disease onset, symptom severity, and cold urticaria threshold values were found to be related to disease evolution ( P < .05). Limitations This study was limited by its retrospective nature. Conclusions The knowledge of the clinical predictors of the disease evolution along with the clinical features of ACU phenotypes would allow for the establishment of an early and proper therapeutic strategy.
Antecedentes: TempTest® es un nuevo método basado en el efecto Peltier, validado para el diagnóstico de pacientes con urticaria por frío (UFr) o por calor (UCal), capaz de medir las variaciones de ...temperatura y la actividad de estas patologías.El objetivo de este estudio es analizar los resultados de las pruebas de provocación utilizando este nuevo método, en pacientes con UFr y UCal seguidos en un Centro de referencia y excelencia para la urticaria (GA2LEN UCARE) en Rio de Janeiro.Metodos: Fueron analizadas los datos de registros médicos de 12 pacientes que tenían antecedentes de UFr o UCaly se sometieron a una prueba de provocación con TempTest®, durante los meses y años de 12/2017 y 02/2020. Las pruebas de provocación de temperatura se realizaron con solicitación para que los pacientes ponen el antebrazo en el elemento de temperatura TempTest® durante 5 minutos. Una respuesta positiva se definió por la aparición de una pápula de 2 mm de estención (el tamaño de elemento de temperatura TempTest®) a los 10 minutos después del desafío, como se recomienda.Resultados: 10 pacientes eran mujeres y 2 hombres, de 13 a 77 años (media = 50,2 años). Entre los 12 pacientes, tenían 3 urticaria por calor y 9 urticaria por frío. Los pacientes diagnosticados con urticaria por calor fueron positivos para temperaturas iguales o superiores a 38 ° C. Entre los pacientes con urticaria por frío, TempTest® fueron positivos para temperaturas iguales o inferiores a 27 ° C.Conclusiones: El TempTest® es, actualmente, lo instrumento más confiable para diagnosticar y monitorear con precisión las enfermedades, siendo sus amplias variaciones de temperatura un factor que debes ser determinado siempre que sea posible, ya que puede ayudar a los pacientes a evitar situaciones de exposición y peligro evitables.
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