Biomarkers to predict therapeutic response in chronic spontaneous urticaria: a review.

Chronic spontaneous urticaria (CSU) is a relatively common dermatological disorder characterized by sudden and unpredictable onset of pruritic wheals and/or angioedema, for more than six weeks. It is a mast cell-mediated histaminergic disorder, considerably worsening patients' quality of life. Current treatment options include anti-histamines, omalizumab and cyclosporine, in a step-wise algorithmic approach, aimed at complete symptom control. Patients do not respond uniformly to these therapeutic options due to phenotypic and endotypic heterogeneity, and often remain uncontrolled/poorly controlled. Recent research is focused on identifying certain biomarkers to predict therapeutic response and facilitate patient-targeted personalized treatment, for maximum benefit. The current article summarizes various biomarkers explored to date, and also elaborates their role in predicting therapeutic response to anti-histamines, omalizumab and cyclosporine, in CSU patients. High disease activity, elevated CRP/ESR and elevated D-dimer are the most important predictors of non/poor-response to antihistamines. Low and very low baseline IgE, elevated CRP/ESR, ASST+, BAT/BHRA+, basopenia, eosinopenia, and elevated D-dimer are predictors of poor and good response to omalizumab and cyclosporine, respectively. Additionally, normal or slightly elevated baseline IgE and FceR1 overexpression are predictors of a faster response with omalizumab. However, none of these predictors have so far been completely validated and are not yet recommended for routine use. Thus, large-scale prospective studies are needed to confirm these predictive biomarkers and identify new ones to achieve the goal of personalized medicine for CSU.

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

Summary: 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.

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.

BACKGROUND: 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. METHOD: 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. RESULT: 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. CONCLUSION: 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.

Time Course of Priming Effect of TF Inducers on Synergistic TF Expression and Intra-Cellular Gap Formation of Human Vascular Endothelial Cells via the Extrinsic Coagulation Cascade.

Chronic spontaneous urticaria (CSU) is characterized by daily recurring wheal and flare with itch for more than 6 weeks. The extrinsic coagulation system has been shown to be activated in correlation with CSU severity. We have reported that tissue factor (TF), a trigger of the extrinsic coagulation cascade, is synergistically expressed on vascular endothelial cells by simultaneous stimulation with TF inducers (TFI), followed by activation of the extrinsic coagulation cascade and hyper permeability in vitro. However, vascular endothelial cells are not likely to be simultaneously stimulated by multiple TFIs under physiological conditions. Therefore, in order to know whether sequential, rather than simultaneous, stimuli with interval may induce synergistic activation of TF, we investigated the time course of the priming effects of each TFI for synergistic TF expression in vascular endothelial cells (HUVECs). We stimulated HUVECs with a TFI (first stimulation) and then stimulated cells with another TFI at indicated time points (second stimulation) and detected TF expression and activity. The TF expression induced by simultaneous stimulation diminished in a few hours. However, both synergistic enhancement of TF expression and activation level of the coagulation cascade were detected even when the second stimulation was added 18 or 22 h after the first stimulation. Thus, the priming effect of TFI for synergistic TF expression may persist for a half day or longer.

Basophil Characteristics as a Marker of the Pathogenesis of Chronic Spontaneous Urticaria in Relation to the Coagulation and Complement Systems.

Chronic spontaneous urticaria (CSU) is a common skin disorder characterized by daily or almost daily recurring skin edema and flare with itch and pruritus anywhere on the body for more than 6 weeks. Although basophil- and mast cell-released inflammatory mediators, such as histamine, play important roles in the pathogenesis of CSU, the detailed underlying mechanism is not clear. Since several auto-antibodies, IgGs which recognize IgE or the high-affinity IgE receptor (FcεRI) and IgEs against other self-antigens, are detected in CSU patients, they are considered to activate both mast cells in the skin and basophils circulating in the blood. In addition, we and other groups demonstrated that the coagulation and complement system also contribute to the development of urticaria. Here, we summarized the behaviors, markers and targets of basophils in relation to the coagulation-complement system, and for the treatment of CSU.

Consecutive injections of low-dose interleukin-2 improve symptoms and disease control in patients with chronic spontaneous urticaria.

PURPOSE: To describe the effectiveness and tolerability of low-dose interleukin (IL)-2 in treating patients with chronic spontaneous urticaria (CSU) refractory to H1-antihistamines. METHODS: This retrospective study included CSU patients who received treatment with at least one cycle of IL-2, injected intramuscularly at a dose of 1.0 million international units daily for 7 consecutive days, after failing treatment with H1-antihistamines. Patients were followed up for ≥12 weeks. RESULTS: Of the 15 patients, 7 (46.7%) and 11 (73.3%) achieved complete response at Week 2 and Week 12, respectively. The mean change of urticaria control test (UCT) and weekly urticaria activity score (UAS7) from baseline was 6.6 (95% CI, 4.2 to 8.9) and - 16.9 (95% CI, -24.0 to -9.8), respectively, at Week 12. Local injection-site reactions were the most common adverse events. No serious adverse events were reported. CONCLUSION: Low-dose IL-2 treatment improves symptoms and disease control for CSU patients refractory to H1-antihistamines.

Possible microRNA-based mechanism underlying relationship between chronic spontaneous urticaria and Blastocystis.

BACKGROUND: Blastocystis spp. has been proposed as a possible cause of extraintestinal clinical signs such as urticaria pathogenesis. OBJECTIVES: The aim of this study was to investigate the differences between microRNA (miRNA) expression profiles of Chronic spontaneous urticaria (CSU) patients in the presence or absence of Blastocystis spp. as well as healthy controls. Additionally, cellular pathways which are affected in the presence of Blastocystis spp. were identified. METHODS: Twenty patients diagnosed with CSU were enrolled in the study and divided into equally two groups according to the presence of Blastocystis spp. Besides, six healthy individuals were included in the study. The expression profiles of 372 human-derived miRNAs have been investigated in serum samples from CSU patients and healthy controls with miScript miRNA PCR Array Human miRBase Profiler. RESULTS: Compared to Blastocystis-negative (BN)-CSU patients, expression of 3 miRNAs (hsa-miR-3183, hsa-miR-4469, hsa-miR-5191) were found to be downregulated by at least two-fold (p < 0.05) in Blastocystis-positive (BP)-CSU patients. Additionally, the miRNA expression profiles of six healthy individuals (n = 3 Blastocystis-positive, n = 3 Blastocystis-negative) were analyzed and it was determined that the expressions of 7 miRNAs (hsa-miR-4661-5p, hsa-miR-4666a-5p, hsa-miR-4803, hsa-miR-5587-5p, hsa-miR-4500, hsa-miR-5680, hsa-miR-382-3p) increased at least 3-fold in the serum of individuals with Blastocystis-positive compared to Blastocystis-negative subjects. Most down-regulated miRNAs, in BP-CSU patients, affect cell adhesion molecules (CAMs), and signaling pathways therefore, Blastocystis spp. presence may influence the clinical presentation of urticaria by leading to unbalanced immunity. In addition, Blastocystis spp. presence may be influenced TGF- ß signaling pathway through altered miRNAs and may be laying the groundwork for the development of CSU in healthy individuals. CONCLUSIONS: As a consequence, this is the first report to show that the miRNA expression profile is affected by the presence of Blastocystis spp. Further miRNA-based studies are needed in order to enlighten the exact underlying molecular mechanisms of the relationship between Blastocystis spp. and CSU.

Basophils activation of patients with chronic spontaneous urticaria in response to C5a despite failure to respond to IgE-mediated stimuli.

Urticaria is characterized by the occurrence of wheals and flares in response to vasoactive mediators, such as histamine. Various studies have suggested the involvement of basophils in the pathogenesis of chronic spontaneous urticaria (CSU). However, histamine release from peripheral basophils in response to stimuli acting on the high affinity IgE receptor (FcϵRI) is impaired in many patients with CSU (non/low responders). We previously demonstrated that tissue factor (TF)s expressed on vascular endothelial cells in response to a combination of various stimuli, such as that of histamine and lipopolysaccharide (LPS), activates the extrinsic coagulation pathway and produces anaphylatoxin, complement 5a (C5a), which then activates basophils and mast cells via the C5a receptor (C5aR). We have revealed that histamine release was induced in response to C5a and formyl-l-methionyl-l-leucyl-l-phenylalanine (fMLP), regardless of the response to anti-IgE antibody, the reduced numbers of basophils and severity of urticaria. Moreover, we found that spontaneous release of histamine ex vivo from basophils of patients with CSU is higher than that from healthy individuals. These results suggest that basophils and the complement system, which could be activated by coagulation factors, may play a critical role in the pathogenesis of CSU, especially in cases refractory to treatment involving the IgE/FcϵRI pathway.

The Role of Crosstalk of Immune Cells in Pathogenesis of Chronic Spontaneous Urticaria.

Chronic spontaneous urticaria (CSU) is defined as recurrent episodes of spontaneous wheal development and/or angioedema for more than six weeks and at least twice a week. The core link in the pathogenesis of CSU is the activation of mast cells, T cells, eosinophils, and other immune cells infiltrating around the small venules of the lesion. Increased vascular permeability, vasodilatation, and recruitment of inflammatory cells directly depend on mast cell mediators' release. Complex regulatory systems tightly influence the critical roles of mast cells in the local microenvironment. The bias toward Th2 inflammation and autoantibodies derived from B cells, histamine expressed by basophils, and initiation of the extrinsic coagulation pathway by eosinophils or monocytes exerts powerful modulatory influences on mast cells. Cell-to-cell interactions between mast cells and eosinophils/T cells also are regulators of their function and may involve CSU's pathomechanism. This review summarizes up-to-date knowledge regarding the crosstalk between mast cells and other immune cells, providing the impetus to develop new research concepts and treatment strategies for CSU.

Integrated Bioinformatics and Validation Reveal IL1B and Its Related Molecules as Potential Biomarkers in Chronic Spontaneous Urticaria.

Background: The etiopathogenesis of chronic spontaneous urticaria (CSU) has not been fully understood, and there has been extensive interest in the interaction between inflammatory dermatosis and pyroptosis. This study intends to investigate the molecular mechanism of pyroptosis-related genes in CSU via bioinformatic ways, aiming at identifying the potential key biomarker. Methods: GSE72540, the RNA expression profile dataset of CSU, was utilized as the training set, and GSE57178 as the validation set. Differently expressed pyroptosis-related genes (DEPRGs), GO, KEGG, and DO analyses were performed. The hub genes were explored by the protein-protein interaction analysis. Moreover, CIBERSORT was employed for estimating immune cell types and proportions. Then, we constructed a DEmRNA-miRNA-DElncRNA ceRNA network and a drug-gene interaction network. Finally, ELISA was used for gene expression analysis. Results: We recognized 17 DEPRGs, whose enrichment analyses showed that they were mostly enriched in inflammatory response and immunomodulation. Moreover, 5 hub genes (IL1B, TNF, and IRF1 are upregulated, HMGB1 and P2RX7 are downregulated) were identified via the PPI network and verified by a validation set. Then immune infiltration analysis displayed that compared with normal tissue, CSU owned a significantly higher proportion of mast cells activated, but a lower proportion of T cells CD4 naive and so on. Furthermore, IL1B was statistically and positively associated with mast cells activated in CSU, and SNHG3, the upstream factor of IL1B in the ceRNA we constructed, also related with mast cells in CSU. Further analysis exhibited that the protein subcellular localization of IL1B was extracellular, according with its intercellular regulation role; IL1B was significantly correlated with key immune checkpoints; and the NOD-like receptor signaling pathway was the mainly involved pathway of IL1B based on the couple databases. What is more, the result of ELISA of CSU patients was the same as the above analyses about IL1B. In addition, the drug-gene interaction network contained 15 potential therapeutic drugs targeting IL1B, and molecular docking might make this relationship viable. Conclusion: IL1B and its related molecules might play a key role in the development of CSU and could be potential biomarkers in CSU.

Altered Gut Microbiota in H1-Antihistamine-Resistant Chronic Spontaneous Urticaria Associates With Systemic Inflammation.

Background and Objective: Chronic spontaneous urticaria (CSU) is a histamine-mediated inflammatory skin disease, and second-generation non-sedating H1-antihistamines (nsAH) at licensed doses have long been the first-line therapy in CSU. However, about 50% of patients are resistant to nsAH, and the precise pathogenesis remains largely unknown but seems to be associated with low-level systemic or intestinal inflammation. We aim to determine the fecal microbial composition and clarify its correlation with the clinical profiles og CSU with nsAH resistance. Methods: A total of 25 CSU patients with or 19 CSU patients without nsAH resistance and 19 healthy controls (HC) were enrolled in this study. The intestinal microbiome was detected by 16S rRNA sequencing. The data were analyzed using R language software. Results: Significantly higher urticarial activity score for 7 days, stool calprotectin, erythrocyte sedimentation rate, serum C-reactive protein, and interleukin-6, but much lower alpha-diversity and evenness of fecal bacterial community were observed in CSU patients with nsAH resistance than in those without (P <0.05 for all variables). Compared to patients with nsAH-responsiveness, the abundance of fecal genera Prevotella, Megamonas, and Escherichia were significantly increased, while that of Blautia, Alistipes, Anaerostipes, and Lachnospira were remarkably reduced in nsAH-resistant patients (uncorrected P <0.05 for all variables). Finally, systemic not intestinal inflammation degree was positively correlated with genera Escherichia, while negatively with genera Blautia, Dorea, Lactobacillus, Eubacterium_hallii_group, and Roseburia. CSU without nsAH resistance and HC individuals showed almost unchanged genera bacterium. Conclusions: Among CSU patients, pro-inflammation phenotype relating to enteric dysbacteriosis features nsAH resistance in CSU patients. The results provide clues for future microbial-based or anti-inflammatory therapies on nsAH resistant CSU.

What Basophil Testing Tells Us About CSU Patients - Results of the CORSA Study.

Basophil testing is the most effective single approach for diagnosing type-IIb autoimmune chronic spontaneous urticaria (TIIbaiCSU). A positive basophil test has been linked to long disease duration, higher disease activity, a poor response to antihistamines and omalizumab, and a better response to cyclosporine and fenebrutinib. As of now it is unclear what other features are connected to a positive basophil test in chronic spontaneous urticaria (CSU). We aimed to identify features of basophil test-positive CSU patients. We performed a cross-sectional study of 85 CSU patients. Basophil testing was done with the basophil activation test (BAT) and the basophil histamine release assay (BHRA). Data were analysed using SPSS: Student's t-test, Chi-square test, Odds Ratio, Spearman's correlation test. Of 85 CSU patients, 44% and 28% tested positive with the BAT and BHRA, respectively. These patients showed higher disease activity and impact, lower levels of disease control and total serum IgE, as well as higher rates of having a positive autologous serum skin test (ASST), angioedema, nocturnal symptoms, symptoms for >5 days/week, and thyroid autoantibodies. The ASST, by itself, was not a good predictor of basophil test results, but it predicted a positive basophil test in up to 100% of cases when combined with angioedema, thyroid autoantibodies or low IgE. In conclusion, a positive basophil test is linked to known features of TIIbaiCSU and novel characteristics including nocturnal symptoms. Further studies on basophil test-positive and -negative CSU patients can help to better understand CSU endotypes and to develop better management approaches.

The Role of Coagulation and Complement Factors for Mast Cell Activation in the Pathogenesis of Chronic Spontaneous Urticaria.

Chronic spontaneous urticaria (CSU) is a common skin disorder characterized by an almost daily recurrence of wheal and flare with itch for more than 6 weeks, in association with the release of stored inflammatory mediators, such as histamine, from skin mast cells and/or peripheral basophils. The involvement of the extrinsic coagulation cascade triggered by tissue factor (TF) and complement factors, such as C3a and C5a, has been implied in the pathogenesis of CSU. However, it has been unclear how the TF-triggered coagulation pathway and complement factors induce the activation of skin mast cells and peripheral basophils in patients with CSU. In this review, we focus on the role of vascular endothelial cells, leukocytes, extrinsic coagulation factors and complement components on TF-induced activation of skin mast cells and peripheral basophils followed by the edema formation clinically recognized as urticaria. These findings suggest that medications targeting activated coagulation factors and/or complement components may represent new and effective treatments for patients with severe and refractory CSU.

Management of Pediatric Chronic Spontaneous Urticaria: A Review of Current Evidence and Guidelines.

Chronic urticaria (CU) is associated with debilitating symptoms such as pruritic wheals and/or angioedema, which can significantly affect patients' sleep, productivity and quality of life. Chronic spontaneous urticaria (CSU) is defined in cases in which no triggering factor is identified. Various guidelines directing the optimal management of CU in the adult population were published and updated over the recent years with the most accepted and widely used being the EAACI/GA2LEN/EDF/WAO 2017 guidelines. Meanwhile, guidelines specific to the pediatric population are scarce, mainly due to the fact that high quality evidence is lacking for many treatment options in this age group. The objective of this article is to review and synthesize the existing literature regarding the management of pediatric CSU. Our review highlights evidence supporting the EAACI/GA2LEN/EDF/WAO 2017 treatment guidelines with non-sedating second-generation antihistamines (sgAHs) as the mainstay of treatment for pediatric CSU, considering their demonstrated efficacy and reassuring safety profile. Additionally, the use of omalizumab in adolescents is well supported by the current literature. There is limited data available regarding the updosing of sgAHs, omalizumab in children with CSU under 12 years of age and the treatment with cyclosporine and leukotriene receptor antagonists (LTRAs) in pediatric patients of all ages. However, the results from currently available case series and case reports are promising for omalizumab and cyclosporine use in children with CSU, although large and well-designed randomized control trials (RCTs) assessing these treatment options are needed in order to formulate strong recommendations for their use. First-generation antihistamines (fgAHs) remain commonly used in pediatric CSU treatment despite a lack of studies assessing their efficacy and safety in the pediatric population and their widely known inferior safety profile compared to sgAHs.

Involvement of Neuro-Immune Interactions in Pruritus With Special Focus on Receptor Expressions.

Pruritus is a common, but very challenging symptom with a wide diversity of underlying causes like dermatological, systemic, neurological and psychiatric diseases. In dermatology, pruritus is the most frequent symptom both in its acute and chronic form (over 6 weeks in duration). Treatment of chronic pruritus often remains challenging. Affected patients who suffer from moderate to severe pruritus have a significantly reduced quality of life. The underlying physiology of pruritus is very complex, involving a diverse network of components in the skin including resident cells such as keratinocytes and sensory neurons as well as transiently infiltrating cells such as certain immune cells. Previous research has established that there is a significant crosstalk among the stratum corneum, nerve fibers and various immune cells, such as keratinocytes, T cells, basophils, eosinophils and mast cells. In this regard, interactions between receptors on cutaneous and spinal neurons or on different immune cells play an important role in the processing of signals which are important for the transmission of pruritus. In this review, we discuss the role of various receptors involved in pruritus and inflammation, such as TRPV1 and TRPA1, IL-31RA and OSMR, TSLPR, PAR-2, NK1R, H1R and H4R, MRGPRs as well as TrkA, with a focus on interaction between nerve fibers and different immune cells. Emerging evidence shows that neuro-immune interactions play a pivotal role in mediating pruritus-associated inflammatory skin diseases such as atopic dermatitis, psoriasis or chronic spontaneous urticaria. Targeting these bidirectional neuro-immune interactions and the involved pruritus-specific receptors is likely to contribute to novel insights into the underlying pathogenesis and targeted treatment options of pruritus.

Gut Microbiome and Serum Metabolome Analyses Identify Unsaturated Fatty Acids and Butanoate Metabolism Induced by Gut Microbiota in Patients With Chronic Spontaneous Urticaria.

Chronic urticaria (CU) is defined as the continuous or intermittent presence of urticaria for a period exceeding 6 weeks and sometimes occurring with angioedema. Between 66 and 93% of patients with CU have chronic spontaneous urticaria (CSU), the precise pathogenesis of which is largely unknown. The aim of this study was to determine the relationship between gut microbiota and serum metabolites and the possible pathogenesis underlying CSU. We collected feces and blood samples from CSU patients and healthy controls and the relationship between gut microbiota and serum metabolites was assessed using 16S rRNA gene sequencing and untargeted metabolomic analyses. The CSU group exhibited decreased alpha diversity of the microbial population compared to the control group. The abundance of unidentified Enterobacteriaceae was increased, while the abundance of Bacteroides, Faecalibacterium, Bifidobacterium, and unidentified Ruminococcaceae was significantly reduced in CSU patients. The serum metabolome analysis revealed altered levels of docosahexaenoic acid, arachidonic acid, glutamate, and succinic acid, suggesting changes in unsaturated fatty acids and the butanoate metabolism pathway. The combined serum metabolomics and gut microbiome datasets were correlated; specifically, docosahexaenoic acid, and arachidonic acid were positively correlated with Bacteroides. We speculate that alterations in gut microbes and metabolites may contribute to exacerbated inflammatory responses and dysregulated immune function with or without regulatory T cell dependence in the pathogenesis of CSU.

Chronic spontaneous urticaria and the extrinsic coagulation system.

Chronic spontaneous urticaria (CSU) is a common skin disorder characterized by daily or almost daily recurring skin edema and flare with itch. Recently, the activation of the blood coagulation cascade has been suggested to be involved in CSU, but the trigger of the coagulation cascade remains unclear. In this article, we review recent understanding of the relationship between the pathogenesis of CSU and extrinsic coagulation reactions. In CSU, vascular endothelial cells and eosinophils may play a role as TF-expressing cells for activating the extrinsic coagulation pathway. Moreover, the expression of TF on endothelial cells is synergistically enhanced by the activation of Toll-like receptors and histamine H1 receptors. The activated coagulation factors may induce plasma extravasation followed by degranulation of skin mast cells and edema formation recognized as wheal in CSU. Molecules involved in this cascade could be a target for new and more effective treatments of urticaria.

Comparative Study of Positive Versus Negative Autologous Serum Skin Test in Chronic Spontaneous Urticaria and its Treatment Outcome.

BACKGROUND: Chronic urticaria (CU) is defined as urticaria persisting daily or almost daily for more than 6 weeks and affecting 0.1% of the population. Mast cell degranulation and histamine release are of central importance in the pathogenesis of CU. About 40-50% of the patients with chronic idiopathic urticaria (CIU) or chronic spontaneous urticaria (CSU) demonstrates an immediate wheal and flare response to intradermal injected autologous serum. This led to the concept of autoimmune urticaria (AIU). AIMS: To determine the occurrence, clinical features, associated clinical conditions, comorbidities of AIU, and to compare this with CSU. This study aimed to find the frequency of autologous serum skin test (ASST)-positive patients among patients with CSU and to identify the clinical and laboratory parameters associated with positive ASST and to compare the treatment outcome. MATERIALS AND METHODS: A prospective correlation study in 110 patients with CSU was conducted, after screening 200 CU patients attending the outpatient Department of Dermatology during from January 2012 to May 2013. Patients were subjected to ASST, complete blood counts, urine routine examination, liver function tests, renal function tests, thyroid function tests (T3, T4, and TSH), and urine analysis. RESULTS: Out of 200 CU patients screened, 90 patients had excludable causes based on detailed history and skin prick test, and the remaining 110 patients were considered to have CSU. These 110 patients were further subjected to ASST, serum immunoglobulin E (IgE), and peripheral blood eosinophilia. ASST was positive in 48 patients and negative in 62 patients. Frequency of urticarial attacks and associated diseases such as abnormal thyroid function tests in both ASST-positive and ASST-negative patients did not show any statistical significance. Only attacks of angioedema in ASST-positive individuals were higher and were statistically significant. In the ASST-positive group, 31 (81.25%) patients showed improvement with first-line antihistamines, along with oral prednisolone and injection Histaglobulin and 10 (10.41%) patients did not show any improvement. Thirty-three (43.54%) patients in the ASST-negative group showed improvement while 13 (30.62%) patients did not show improvement. CONCLUSION: ASST is considered a screening test for AIU, which decreases the rate of diagnosis of idiopathic form of CU. ASST-positive patients in addition to antihistamines, were treated with short course of oral steroids and weekly Histaglobulin injections for 5 weeks followed by the 3(rd) and 6(th) months.