Severe Chronic Spontaneous Urticaria Research Articles

Increased Neutrophil-Lymphocyte Ratio and Platelet-Lymphocyte Ratio in Chronic and Severe Urticaria.

Chronic spontaneous urticaria (CSU) is a disturbing skin condition often severely detrimental to quality of life. Haematological markers of inflammation such as neutrophil-to-lymphocyte and platelet-to-lymphocyte may be used in the assessment of inflammatory skin diseases. Their usefulness in urticaria is unknown. Neutrophil- to-lymphocyte, platelet-to-lymphocyte, and total serum IgE were investigated in urticaria patients: acute spontaneous urticaria (ASU) versus CSU, children versus adults with CSU, and patients with mild-to-moderate versus severe CSU. This retrospective cohort study included patients of all ages diagnosed with urticaria between 2005 and 2020 and blood counts within 30 days of diagnosis. Patients with comorbidities influencing blood cells (infection, surgery, malignancy) were excluded. Neutrophil-to-lymphocyte and platelet-to-lymphocyte were evaluated in patients with ASU vs CSU and mild-to-moderate CSU vs severe CSU (defined by the use of systemic medications or hospitalizations). A total of 13,541 urticaria patients were included in the study. CSU patients (n = 5,021) had higher neutrophil-to-lymphocyte and platelet-to-lymphocyte, as well as serum IgE levels compared with ASU patients (n = 8,520). Adults had higher neutrophil-to-lymphocyte and platelet-to-lymphocyte than children. Severely affected patients (n = 53) had higher neutrophil-to-lymphocyte and platelet-to-lymphocyte compared with mild-to-moderately affected patients (n = 4,968). Patients with higher neutrophil-to-lymphocyte and platelet-to-lymphocyte had higher odds of having CSU rather than ASU and severe urticaria rather mild-to-moderate. In conclusion, neutrophil-to-lymphocyte and platelet-to-lymphocyte are simple and available markers that can be used to predict and assess severe and chronic urticaria.

The autologous serum skin test (ASST) predicts the response to anti-IgE treatment in Chronic Spontaneous Urticaria patients: a prospective study.

Background. Chronic spontaneous urticaria (CSU), characterized by recurrent itchy wheals and angioedema for > 6 weeks, is a quite common disease that may heavily impair the quality of life. Omalizumab, an anti-IgE mAb, has much improved the management of CSU but patients' response to the drug may vary and predictive markers are still largely missing. We investigated the predictive value of the autologous serum skin test (ASST) on omalizumab response. Methods. 15 patients with severe CSU eligible for omalizumab treatment were prospectively studied submitting them to ASST and to complete blood count, D-dimer, anti-thyroid peroxidase antibodies, and total IgE measurement before the start of the treatment. Results. 14/15 (93%) responded brilliantly to omalizumab at 3 months assessment. 7 responded in less than 1 month ("early responders") and 7 only after multiple administrations ("late responders"). Of 9 patients scoring positive on ASST, 7 (78%) were late, and 2 (22%) early responders to omalizumab (p = 0.021). Of 6 patients scoring negative on ASST, 5 were early omalizumab responders and 1 did not respond. The PPV and NPV of the ASST for a "late" response to omalizumab were 78% and 100%, respectively. Total IgE were significantly higher in early responders. Conclusions. Although larger prospective studies are needed to confirm these results, this study confirms previous retrospective investigations that the positive ASST appears to predict a slow response to omalizumab in CSU patients.

Biomarkers predicting the controller dose of omalizumab in patients with chronic spontaneous urticaria.

Clinical trials showed the efficacy of 300 mg/4 weeks of omalizumab (OMA) during 6 months in patients with severe chronic spontaneous urticaria (CSU). Nevertheless, in real life, many patients require higher doses and/or longer treatment. This study assesses the real-life performance of OMA in severe CSU and identifies factors associated with the response. CSU patients eligible for OMA were recruited prospectively. Clinical data and a blood test were collected before OMA initiation. Urticaria Activity Score 7 (UAS7) was calculated at baseline and every 3 months during OMA treatment. CSU control was defined as UAS7 <7 points. This work was partially sponsored by OMA manufacturer. Eighty-nine adults (19.1% males) with severe CSU were recruited. Median duration of CSU prior to OMA initiation was 2 years, and median severity by UAS7 at baseline was 24 points (range 10-42 points). OMA controlled 94.4% of patients, but 17.9% of responders required doses >300 mg/4 weeks. A blood basophil count >20 cells/μL (OR 13.33; 95% CI 3.32-52.63; p < .001) and the absence of hypothyroidism (OR 3.65; 95% CI 0.78-16.95; p = .099) were identified as predictive factors to achieve control with 300 mg/4 weeks. Twelve patients were able to stop OMA during the study (responders in remission, RR). RR had received OMA for a median of 29 months (12-53 months). Conversely, 32 patients had been on OMA for >29 months at the end of the study (active responders, AR). AR had received OMA for a median of 45 months (30-100 months). There were no significant differences in clinical or analytical factors between RR and AR patients. Low blood basophil count and the presence of hypothyroidism might serve as biomarkers for the controller dose of OMA in severe CSU patients.

A targeted amplicon next-generation sequencing assay for tryptase genotyping to support personalized therapy in mast cell-related disorders.

Tryptase, the most abundant mast cell granule protein, is elevated in severe asthma patients independent of type 2 inflammation status. Higher active β tryptase allele counts are associated with higher levels of peripheral tryptase and lower clinical benefit from anti-IgE therapies. Tryptase is a therapeutic target of interest in severe asthma and chronic spontaneous urticaria. Active and inactive allele counts may enable stratification to assess response to therapies in asthmatic patient subpopulations. Tryptase gene loci TPSAB1 and TPSB2 have high levels of sequence identity, which makes genotyping a challenging task. Here, we report a targeted next-generation sequencing (NGS) assay and downstream bioinformatics analysis for determining polymorphisms at tryptase TPSAB1 and TPSB2 loci. Machine learning modeling using multiple polymorphisms in the tryptase loci was used to improve the accuracy of genotyping calls. The assay was tested and qualified on DNA extracted from whole blood of healthy donors and asthma patients, achieving accuracy of 96%, 96% and 94% for estimation of inactive α and βΙΙΙFS tryptase alleles and α duplication on TPSAB1, respectively. The reported NGS assay is a cost-effective method that is more efficient than Sanger sequencing and provides coverage to evaluate known as well as unreported tryptase polymorphisms.

Management of severe chronic spontaneous urticaria with omalizumab

Management of severe chronic spontaneous urticaria with omalizumab

The Efficacy and Safety of High Dose (10 mg) of Desloratadine (Dazit® 10) in the Treatment of Chronic Spontaneous Urticaria in India: A Phase III, Multicentric, Open-Label, Single-Arm Study.

Chronic spontaneous urticaria (CSU) is a debilitating affliction that affects diverse quality of life (QoL) parameters such as sleep, self-esteem, and daily activities. Second-generation antihistamines, such as desloratadine, are more effective and safer in managing CSU. Desloratadine is a nonsedating, potent, and highly selective H1 receptor antagonist. At its daily dose of 5 mg, almost half of CSU patients do not show symptomatic improvement. European Academy of Allergy and Clinical Immunology (EAACI)/Global Allergy and Asthma European Network (GA2LEN)/European Dermatology Forum (EDF) (EuroGuiDerm)/Asia Pacific Association of Allergy, Asthma and Clinical Immunology (APAAACI) guidelines recommend increasing the dosage to up to four times in such nonresponsive patients. However, there is insufficient clinical evidence in Indian settings. We evaluated the efficacy and safety of 10 mg desloratadine (OD) in 256 nonresponsive patients with moderate to severe CSU. The primary outcome was the change in Urticaria Activity Score (UAS7) from baseline to four weeks. Additionally, change in Chronic Urticaria Quality of Life (CU-Q2oL) scores during the course of treatment was also evaluated. The mean UAS7 scores showed a significant reduction from 31.9 ± 4.8 at baseline to 18.2 ± 8.1 at the end of the study (p < 0.0001). The use of a higher dose of desloratadine also decreased the CU-Q2oL scores significantly from 59.8 ± 14.7 at baseline to 35.4 ± 10 at four weeks (p < 0.0001). The incidence of adverse events (AEs) possibly linked to the drug was low (1.6%), and no serious adverse events were reported. Results indicated improvements in the disease severity as well as its positive impact on participants' QoL. This study confirms the efficacy and safety of daily use of a twofold dose of desloratadine in nonresponsive moderate to severe CSU patients.

Safety of omalizumab in chronic urticaria during pregnancy: a real-life study.

Managing a pregnant patient with chronic spontaneous urticaria (CSU) is often challenging. Recent data have shown that most CSU treatments in pregnant patients are second-generation H1 antihistamines (sgAHs), while data on the safety of omalizumab are scant. To evaluate, in a routine clinical practice setting, the efficacy and safety of omalizumab in patients with severe CSU refractory to sgAHs who either became pregnant during treatment or who started the drug during pregnancy. We conducted a retrospective study of women aged ≥ 18 years who were pregnant, who received one or more doses of omalizumab at any time during their pregnancy or who were taking omalizumab at the time of, or in the 8 weeks before, conception. Twenty-nine pregnant patients were evaluated: 23 (79%) conceived a child while taking omalizumab (group A), while 6 (21%) started omalizumab treatment during pregnancy (group B). Among patients in group A, we observed 23 births (21 liveborn singletons and 1 liveborn twin pair) and 1 miscarriage. Fifteen (65%) patients discontinued omalizumab after confirming their pregnancy, while eight (35%) were exposed to omalizumab during their entire pregnancy. In group B, omalizumab was introduced at a mean (SD) 10.83 (3.60) weeks' gestation and all patients were exposed to it until the end of pregnancy. In this group, there were seven liveborn infants (five singletons and one twin pair). No adverse events, pregnancy complications or congenital anomalies in newborns were recorded in either group. Omalizumab for CSU treatment before and during pregnancy does not appear to have negative effects on maternal or fetal outcomes.

Comparative analysis of clinical efficacy and safety of omalizumab biosimilar in the treatment of patients with chronic spontaneous urticaria

BACKGROUND: Importance of optimizing strategy for treatment of chronic spontaneous urticaria is highly becoming relevance for the clinicians. Nowadays monoclonal antibodies are preferred option of treatment the refractory chronic spontaneous urticaria, main of that is omalizumab.&#x0D; AIM: to establish comparative analysis of the efficacy and safety of Genolair (JSC Generium, Russia) and Xolair (Novartis Pharma AG, Switzerland) in the treatment of patients with chronic spontaneous urticaria.&#x0D; MATERIALS AND METHODS: A 36-week, open parallel-group study was conducted. Were included 43 adult patients with chronic spontaneous urticaria who were resistant to ongoing therapy with standard and escalated doses of second-generation H1-antihistamines. All patients were divided into 2 groups: the main group (MG; n=18) ― patients who administrated Genolair; the comparison group (CG; n=25) ― patients who firstly administrated Xolair and then switching therapy to Genolair. Throughout the study period, patients completed questionnaires on the assessment of disease activity (UAS 7), urticaria control (UCT), quality of life index (DLQI). Additionally, the level of total IgE in blood serum was assessed. For statistical data processing, EXCEL 2010 and STATISTICA 7.0 software packages were used.&#x0D; RESULTS: After 4 weeks from the start of monoclonal antibody therapy, patients in both groups were responders to omalizumab. At the same time, there were no significant differences when comparing scores on the UAS 7, UCT scale between patients of the MG and the CG during the entire observation period (p 0.05). The change in treatment paradigm in CG also did not have a statistically significant effect on the indicators of urticaria activity and disease control (p 0.05). At the same time, the quality of everyday life changed more positively in the MG, which was reflected in a more pronounced change in the DLQI index at the time of the control assessment since 20 weeks of therapy (p=0.032). An increase in the level of total IgE in the blood serum of all patients with chronic spontaneous urticaria after the initiation of a course of immunobiological therapy was demonstrated, while there were no statistically significant intergroup differences in relation to changes in this laboratory parameter (p 0.05).&#x0D; CONCLUSION: During the treatment of patients with severe chronic spontaneous urticaria, resistant to ongoing therapy with standard and escalated doses of second-generation H1-antihistamines, comparable clinical efficacy and safety of the study drug Genolair and the reference drug Xolair were shown.

Real-Life Data on the Use of Omalizumab in Patients with Severe Asthma and Chronic Urticaria and Mepolizumab in Patients with Severe Asthma: A Retrospective Study

This study aimed to assess the real-life effectiveness of omalizumab and mepolizumab in patients with severe asthma and chronic spontaneous urticaria (CSU), explicitly examining changes in IgE levels and eosinophil counts during treatment. This retrospective study involved patients with severe asthma or CSU treated with biologic agents, including omalizumab and mepolizumab. The primary outcome measures were serum IgE levels, eosinophil counts, urticaria activity scores (UAS), and asthma control test scores (ACT). We studied 61 patients with severe asthma or chronic urticaria treated with biological agents. Patients with asthma exhibited a significant reduction in the median annual attack rate from 4 to 0 with omalizumab (p&amp;lt;0.001) and from 6 to 1 with mepolizumab (p&amp;lt;0.001). Eosinophil counts, and ACT scores significantly decreased with mepolizumab (p&amp;lt;0.001). Six patients who transitioned from omalizumab to mepolizumab did not experience severe asthma attacks in the first six months following the treatment switch. Patients with CSU showed a significant response to omalizumab (p&amp;lt;0.001). We observed significant improvements in various markers, including total IgE levels, eosinophil counts, UAS, and ACT scores, indicating that these treatments can effectively manage the symptoms of both conditions. These findings underscore the potential benefits of using these treatments as effective therapeutic options.

Long-Term Safety of Omalizumab in Children with Asthma and/or Chronic Spontaneous Urticaria: A 4-Year Prospective Study in Real Life.

Background: Insufficient data are available on the long-term "real-life" safety profile of omalizumab in children. This study evaluated the long-term safety of omalizumab in a pediatric cohort with severe asthma or chronic spontaneous urticaria (CSU). Methods: A monocentric, prospective study evaluated the long-term safety of omalizumab in patients aged 6-18 years. Each patient completed the standardized MedDRA questionnaire to identify adverse events (AEs). Results: In total, 23 patients, median age 15 (14-18) years, affected by severe asthma (60.8%) or CSU (39.2%), treated with omalizumab for 2 (1-4) years were enrolled. The most common AEs belong to the system organ class (SOC) of general disorders and administration-site conditions (37.17%). Skin and subcutaneous tissue problems represent the second most frequently reported AEs (24.35%). Central nervous system and musculoskeletal disorders were quite frequent (15.38% and 8.97%, respectively). Other adverse events were tachycardia (5.12%), vertigo and abdominal pain (2.60% and 3.86%, respectively), and dry eye (1.3%). Only one patient reported herpes virus infection during treatment (1.3%). No cases of anaphylaxis, hemopathies, uronephropathies, respiratory, psychiatric, hepatobiliary, or oncological pathologies were reported. Conclusions: Long-term "real-life" treatment with omalizumab in children appears well tolerated. Its safety and efficacy profile makes omalizumab an excellent alternative in severe asthma and CSU in children.

Thyroid Autoimmunity in CSU: A Potential Marker of Omalizumab Response?

The response of severe chronic spontaneous urticaria (CSU) to omalizumab largely depends on the autoimmune or autoallergic endotype of the disease. Whether thyroid autoimmunity may predict omalizumab response along with total IgE in CSU is still unclear. Three hundred and eighty-five patients (M/F 123/262; mean age 49.5 years; range 12-87 years) with severe CSU were studied. Total IgE levels and thyroid autoimmunity (levels of anti-thyroid peroxidase [TPO] IgG) were measured before omalizumab treatment. Based on the clinical response, patients were divided into early (ER), late (LR), partial (PR) and non (NR) responders to omalizumab. Thyroid autoimmunity was detected in 92/385 (24%) patients. Altogether, 52%, 22%, 16% and 10% of patients were ER, LR, PR and NR to omalizumab, respectively. Response to omalizumab was not associated with thyroid autoimmunity (p = 0.77). Conversely, we found a strongly positive association between IgE levels and omalizumab response (p < 0.0001); this association was largely driven by early response (OR = 5.46; 95% CI: 2.23-13.3). Moreover, the predicted probabilities of early response strongly increased with increasing IgE levels. Thyroid autoimmunity alone cannot be used as a clinical predictor of omalizumab response. Total IgE levels remain the only and most reliable prognostic marker for omalizumab response in patients with severe CSU.

Hong Kong-Macau Severe Hives and Angioedema Referral Pathway.

Urticaria (defined as the presence of hives, angioedema, or both) can be caused by a variety of etiologies ranging from more common conditions such as chronic spontaneous urticaria (CSU) to rarer conditions such as hereditary angioedema (HAE). Specialist referral may be necessary in cases of severe urticaria or HAE, but access to specialist services remains limited in certain regions, such as the Greater Bay Area (GBA) of China. To address this, the Hong Kong-Macau Severe Hives and Angioedema Referral Pathway (SHARP) was initiated by the Hong Kong Institute of Allergy and Macau Society of Dermatology to promote multidisciplinary collaboration and regional exchange of expertise in the diagnosis and management of severe urticaria. A nominated task force of dermatologists and immunologists who manage patients with severe urticaria formulated the consensus statements (CS) using the Delphi method. The consensus was defined a priori as an agreement of ≥80%. A total of 24 CS were formulated, including four statements on classifications and definitions, seven statements on diagnosis, and 13 statements on management and referral. The definitions for acute/chronic urticaria and severe CSU were stated. Unnecessary investigations and inappropriate medications were discouraged. The characteristics and recommended approach to suspected bradykinergic angioedema were specified. Stepwise treatment options using second-generation antihistamines, omalizumab, or cyclosporin for patients with CSU were addressed, and the importance of access to HAE-specific medications was emphasized. Furthermore, an integrated referral pathway for patients with severe hives and angioedema was constructed. The SHARP provides guidance for the management and specialist referral of patients with severe hives and angioedema in Hong Kong and Macau.

Ефективність та безпечність підготовки до вакцинації проти вірусу SARS-COV-2 у пацієнтів із хронічною рецидивуючою кропив’янкою

Abstract. The aim: to develop a personalized algorithm for vaccination against COVID-19 for patients with severe chronic urticaria and to evaluate its effectiveness and safety. Methods. Patients with severe (according to the UAS7 scale) chronic spontaneous urticaria and concomitant gastroenterological pathology, who were observed at the City Allergology Center, were included in a prospective single-center clinical study. All patients underwent a complete physical examination, evaluation of complaints, history of life and illness, presence of concomitant pathology. Patients with a history of COVID19 or complete or partial vaccination against COVID-19 were excluded from the study. Blood tryptase level was determined before vaccination using immunofluoroenzymatic analysis (ImmunoCAP). Total serum IgE was determined using an immunochemical method. Preparation for vaccination against the SARS-COV-2 virus was carried out according to the developed algorithm: the appointment of 5 mg of desloratadine orally 30 minutes before vaccination with a normal level of tryptase (&lt; 11 ng/l); and 20 mg of desloratadine 30 minutes before vaccination at an elevated level of tryptase (≥ 11 ng/L) with further observation of the condition of patients during the day after vaccination. Results. The study included 30 patients aged 24 to 63 years, median age 52 (39-59) years, of which 66.7 % were women. The duration of the disease was, on average, 6 years, and 63.3 % of patients suffered from urticaria for five or more years. All 100 % of patients had a severe course of chronic urticaria: from 28 to 42 points on the UAS7 scale, median 42 (42-42) points. Among patients with severe chronic urticaria and concomitant gastrointestinal pathology included in the study, 60 % had elevated serum tryptase levels, were older and had a higher prevalence of H. pylori infection, but a lower prevalence of concomitant allergic pathology. The level of tryptase did not correlate with the level of total IgE. Conclusions The developed individual algorithm for pre-vaccination preparation of patients with severe chronic urticaria has shown its effectiveness and safety in preparing such a difficult category of patients for vaccination against SARS-CoV-2 infection, which is vital today.

Omalizumab and allergen immunotherapy for respiratory allergies: A mini-review from the Allergen-Immunotherapy Committee of the Italian Society of Pediatric Allergy and Immunology (SIAIP).

Although currently approved to treat severe asthma and chronic spontaneous urticaria, omalizumab has also been an effective and safe add-on treatment for other allergic diseases. Namely, omalizumab has been proposed to be used as add-on therapy in patients with allergic rhinitis and asthma and undergoing specific allergen immunotherapy (AIT). AIT is the only treatment that modifies the natural history of IgE-mediated diseases. This brief review summarizes the available evidence and controversies on the efficacy and safety of omalizumab combined with specific AIT.

Current and Future Approaches in Management of Chronic Spontaneous Urticaria Using Anti-IgE Antibodies.

Chronic spontaneous urticaria (CSU) considerably alters patients’ quality of life, often for extended periods, due to pruriginous skin lesions, impaired sleep, unexpected development of angioedema, and failure of conventional treatments in properly controlling signs and symptoms. Recent research focused on the development of new therapeutic agents with higher efficacy. Although the production of specific immunoglobulin E (IgE) antibodies against certain allergens is not a characteristic of the disease, treatment with omalizumab, a monoclonal anti-IgE antibody, proved efficient and safe in patients with moderate to severe chronic spontaneous urticaria uncontrolled by H1-antihistamines. Ligelizumab, a high-affinity monoclonal anti-IgE antibody, may also efficiently relieve symptoms of unresponsive chronic urticaria to standard therapies. This comprehensive review aims to present recently acquired knowledge on managing chronic spontaneous urticaria with new anti-IgE antibodies. We conducted extensive research on the main databases (PubMed, Google Scholar, and Web of Science) with no restrictions on the years covered, using the search terms “anti-IgE antibodies”, “omalizumab”, “ligelizumab”, and “chronic spontaneous urticaria”. The inclusion criteria were English written articles, and the exclusion criteria were animal-related studies. ClinicalTrials.gov was also reviewed for recent relevant clinical trials related to CSU treatment. CSU is a challenging disease with a significant effect on patients’ quality of life. Current therapies often fail to control signs and symptoms, and additional treatment is needed. New biologic therapies against IgE antibodies and FcεRIα receptors are currently under investigation in advanced clinical trials. We reviewed recently published data on CSU management using these novel treatments. The development of new and improved treatments for CSU will lead to a more personalized therapeutical approach for patients and provide guidance for physicians in better understanding disease mechanisms. However, some agents are still in clinical trials, and more research is needed to establish the safety and efficacy of these treatments.

Nonsteroidal anti-inflammatory drugs hypersensitivity in chronic spontaneous urticaria in the light of its pathogenesis.

Up to 15% of patients with chronic spontaneous urticaria (CSU) experience severe exacerbations of their baseline cutaneous disease after taking nonsteroidal anti-inflammatory drugs that inhibit cycloxygenase-1 (COX-1) enzyme. These subjects are defined as having a NECD (NSAID-exacerbated cutaneous disease). The way NSAID hypersensitivity correlates with the different pathogenic mechanisms of CSU has not been investigated so far. 235 adults with severe CSU submitted to omalizumab treatment were studied. A rapid omalizumab response was considered as a marker of auto-allergic (Type I) CSU whereas patients showing a slow response or not responding at all were regarded as having a type IIb autoimmune disease. At the first visit medical history of tolerance to aspirin and/or other COX-1 inhibiting NSAID was ascertained. Duration of disease, atopic status, thyroid autoimmunity, CRP, D-dimer plasma levels, and total IgE were assessed appropriately. 23 (10%) were hypersensitive to NSAID. Patients with or without did not differ in any of the variable considered, and a similar proportion in the two groups showed type I or type IIb CSU. The study suggests that in CSU hypersensitivity to NSAID represents a phenomenon that is independent on the pathogenesis of the underlying skin disease.

Clinical variables of severe chronic spontaneous urticaria from total IgE standpoint: a retrospective study

Background.Baseline total IgE levels have recently emerged as a prognostic factor for the clinical response to omalizumab in patients with severe chronic spontaneous urticaria (CSU). Objective. To investigate the main clinical features of patients with severe CSU from the standpoint of baseline total IgE. Methods. 153 patients (M/F 52/101; mean age 49,7 years) with severe CSU were studied. Based on IgE levels patients were divided into 5 subgroups and a ROC curve was built to define a threshold level for omalizumab response. Atopic status, thyroid autoimmunity, activation of the coagulation cascade, and response to omalizumab were studied as well. Results. The subgroups did not differ in terms of age and gender. Atopy prevailed in the subgroup showing elevated IgE. Thyroid autoimmunity and elevated D-dimer levels were similarly distributed in the five subgroups. 94 patients showed a prompt response to omalizumab. The likelihood of a prompt response was higher in males (p less than 0.01). In the subgroup showing the lowest IgE levels only 10% responded promptly to the drug; these proportions were 60%, 65%, 81% and 83% in the remaining groups. 66% of those in group A did not respond at all to omalizumab. A threshold IgE level of 18 IU/ml was detected for omalizumab response. Conclusions. Baseline total IgE show a high high prognostic value for omalizumab response with a threshold level of 18 IU/ml. Males seem more responsive to omalizumab. Most patients show a mixed clinical picture where signs of atopic status co-exist with signs of an autoimmune disease.

A comparison of autologous serum, plasma, and whole blood for intradermal autoreactivity testing in patients with chronic spontaneous urticarial: A cross-sectional study

Background: Autologous serum (ASST) and plasma (APST) skin testing confirm autoreactivity in chronic spontaneous urticaria (CSU). Whole blood autohemotherapy has been used. Plasma and even whole blood may be used instead of serum with relatively quicker preparation and cheaper method especially using the latter in centers with limited resources. Purpose: The purpose of the study is to determine if similar intradermal skin reactions can be observed when using either serum, plasma, or whole blood in autologous skin tests and to determine factors associated with positive tests and wheal diameter. Methods: We performed a cross-sectional study of chronic urticaria patients in a dermatology clinic. Tests were performed according to EAACI/GA2 LEN Task Force recommendations. Urticaria Activity Score over 7 days (UAS7) was assessed. Statistical analyses included Chi-square, Mann–Whitney U, Spearman's, and Wilcoxon rank tests. Results: Twenty-six (77%) females and 8 (24%) males mean age 34 (26–42) years participated. ASST, APST and autologous whole blood for skin testing (AWBST) positivity rates were 24%, 29% and 27%, respectively (P = 0.86). 13 (38%) had at least 1 positive test; all tests were negative in 21 (62%). All tests were positive in 7 (21%), 3 (23%) were positive APST alone, 2 (15%) AWBST, 1 (8%) ASST. Pretest UAS7 was higher with those with test positive (P = 0.04). Test results were unaffected by age, gender, disease duration, atopy, anti-nuclear antibody, and thyroid status. Wheal diameter correlated with thyroid-stimulating hormone (P = 0.04). Conclusion: Autoreactivity rates were similar with ASST, APST, and AWBST. Positive tests were associated with severe CSU. Autologous whole blood may be a simpler and less costly alternative to plasma and serum for autoreactivity skin testing in patients with chronic urticaria.

Analysis of clinical factors as possible predictors of response to omalizumab and relapse after treatment discontinuation in chronic spontaneous urticaria.

Omalizumab is a monoclonal anti-IgE antibody which is effective in chronic spontaneous urticaria (CSU), although clinical response appears to be variable in the real-life setting. The aim of this study was to evaluate whether the response of CSU to omalizumab and disease relapse are associated with individual and/or clinical characteristics of patients. We retrospectively evaluated the clinical records of 124 patients treated with omalizumab for moderate to severe CSU refractory to antihistamines. Disease activity was assessed using the urticaria activity score over the last 7 days (UAS7). After 24 weeks of treatment, 91% of patients showed complete remission (UAS7=0) or good control (UAS7 < 7) of CSU. Omalizumab was re-administered in 45 patients because of recurrence of moderate to severe symptoms at week 8 after treatment discontinuation or later, and clinical results achieved with retreatment were similar to those observed in the first course. Among the parameters included in our analysis (age and sex of patients, documented history of atopy or autoimmune thyroid disease, CSU duration and baseline severity, concurrent angioedema, and association with chronic inducible urticaria), none was associated with response to omalizumab in our study population. Similarly, these parameters did not significantly differ between patients who experienced CSU relapse and those without relapse. Predictors of response to omalizumab treatment in CSU patients are still unclear, and further studies are needed to evaluate the presence of baseline factors that can influence treatment outcome.

Omalizumab in severe chronic urticaria: are slow and non-responders different?

Background. The response to Omalizumab by patients with severe Chronic Spontaneous Urticaria (CSU), may be rapid, slow, or absent. An early response has been associated with an IgE-mediated auto-allergic pathogenic mechanism, whereas little is known about slow and non-responders. Objective. To compare CSU patients responding slowly or non-responding to Omalizumab. Methods. Forty-six patients showing a slow (n= 23) or absent (n= 23) response to Omalizumab out of a cohort of 170 patients with severe CSU (UAS-7 major 30) were studied. Several baseline clinical and serological parameters were compared in the two groups. Results. Apart from a lower prevalence of atopic diseases (p minor 0.05) and a slightly higher prevalence of thyroid autoimmunity in non-responders, the two groups were similar in terms of clinical and serological features. The majority of patients in both groups showed low baseline total IgE levels. Conclusions. Patients with severe CSU showing a slow response or not responding at all to omalizumab show impressive similarities. It is currently not possible to predict whether patients with severe CSU and low IgE levels will show a slow response or will not respond to anti-IgE treatment.