INTRODUCTION

Chronic spontaneous urticaria (CSU) represents a complex and challenging dermatological disorder characterized by recurrent, transient, and pruritic wheals that persist for more than six weeks without any identifiable known external trigger. This condition significantly impacts the patient’s quality of life, causing substantial physical discomfort and psychological distress. The pathogenesis of CSU is multifaceted, involving intricate immunological mechanisms that remain only partially understood, highlighting the critical need for comprehensive research into its clinical and immunological characteristics [1].

The immunopathological landscape of CSU is predominantly governed by autoimmune processes, with emerging evidence suggesting the involvement of multiple immunological pathways. Autoantibodies against high-affinity IgE receptors (FcεRIα) and interleukin-6 (IL-6) have been increasingly recognized as potential key mediators in disease progression [2]. These autoimmune phenomena trigger mast cell and basophil activation, leading to excessive histamine release and subsequent inflammatory cascades that manifest as urticarial lesions [3].

Immunological biomarkers have shown potential as valuable tools for diagnosing and predicting outcomes in the complex pathogenesis of CSU. Specific immunological biomarkers such as interleukin 6 (IL-6), total Immunoglobulin E (IgE), anti-thyroid peroxidase antibodies (anti-TPO) and various cytokine profiles have demonstrated a potential role in understanding disease mechanisms and predicting treatment responses [4]. This research aims to systematically investigate the relationships between clinical manifestations and immunological biomarkers in CSU patients by conducting a comprehensive analysis of immunological biomarkers and clinical indicators to identify a possible correlation and prognostic indicators.

MATERIALS AND METHODS

The sample size was calculated considering the number of patients attending the outpatient department (OPD) of dermatology, which was approximately 3 to 4 per week on average.

According to the Yamane formula, a sample size of 100 with 50 cases clinically diagnosed as chronic spontaneous urticaria and 50 age- and sex-matched controls was enrolled. Before enrolment, bilingual and well-informed written consent was obtained from all participants.

Detailed demographic profiles, medical histories, and a thorough physical examination were documented. Disease severity was assessed using the Urticaria Activity Score (UAS7) from the Australasian Society of Clinical Immunology and Allergy CSU Guidelines. Patients on immunomodulatory drugs within the past four weeks, those with other types of chronic inducible urticaria, pregnant and lactating mothers, and those with chronic inflammatory or connective tissue disorders were excluded.

Venous blood samples were collected in clot activator tubes, and sera were separated and stored at 80°C till the time of estimation and were analyzed for various biomarkers, including interleukin 6 (IL-6), total immunoglobulin E (IgE), and anti-thyroid peroxidase antibodies (anti-TPO). The biomarkers were quantified using commercially available enzyme-linked immunosorbent assay (ELISA) kits (Invitrogen by Thermo Fisher Scientific, Life Technologies, Frederick, U.S.) following the manufacturer’s instructions at the central research laboratory. The calibration curves were plotted on semi-log papers and values of the optical density of the samples were calculated from the standard curve for the ELISA kit.

RESULTS

This case-control study included 50 patients with confirmed chronic spontaneous urticaria (CSU) and 50 healthy controls.

Table 1 presents the fundamental demographic profile of the study population, including age distribution, sex ratio, and disease characteristics. The majority of the participants in both groups were young adults (20–40 years), with a notably equal sex distribution in the CSU group. Disease severity assessment revealed that 72% of the CSU patients presented with a severe disease (UAS 16–42), while 28% had moderate symptoms (UAS 7–15). Disease duration analysis showed that most of the patients (62%) had experienced symptoms for less than five years, with smaller proportions having longer-standing disease. No significant differences were observed in the age and sex distribution between the cases and controls, ensuring demographic comparability between the groups.

Table 1: Demographic and clinical characteristics.

Table 2 highlights the significant alterations in immunological markers in CSU patients when compared to healthy controls. Mean IL-6 levels were significantly higher in CSU patients (9.1 ± 5.1 pg/mL) compared to controls (3.12 ± 2.8 pg/mL, p = 0.004). While anti-TPO antibody levels were elevated in CSU patients (78.9 ± 164.7 IU/mL vs. 45.2 ± 142.3 IU/mL in controls), this difference did not reach a statistical significance (p = 0.27). Total IgE levels were notably elevated in CSU patients (212.6 ± 239.8 IU/mL) when compared to healthy controls (67.8 ± 72.3 IU/mL, p < 0.001), suggesting a substantial involvement of IgE-mediated mechanisms in CSU pathogenesis.

Table 2: Immunological biomarkers.

Table 3 demonstrates the correlation between disease severity (UAS score) and various biomarkers, providing insight into potential disease activity indicators. IL-6 demonstrated the most pronounced correlation, increasing more than threefold from 3.12 ± 2.8 pg/mL in controls to 10.3 ± 4.9 pg/mL in severe cases (p < 0.001). Total IgE showed a dramatic increase corresponding to disease severity, rising from 67.8 ± 72.3 IU/mL in controls to 257 ± 268.7 IU/mL in severe chronic spontaneous urticaria cases (p < 0.001). While anti-TPO levels increased with disease severity, this trend was not statistically significant (p = 0.54). These findings collectively identify IL-6 and total IgE as potential biomarkers for monitoring disease activity in CSU.

Table 3: Association of UAS with biomarkers.

DISCUSSION

Our study demonstrated significant alterations in immunological markers in patients with CSU when compared to the healthy controls. The disease duration analysis revealed that most patients (62%) had experienced symptoms for less than five years, which was consistent with findings by Maurer et al. [2], who reported approx. 70% of CSU patients experiencing symptoms for 1–5 years. The sex distribution was balanced (50% each), which differed slightly from previous studies, such as that by Kolkhir et al. [3], which reported a female predominance.

The demographic profile of our study population showed a predominance of young adults (20–40 years), constituting 66% of cases, which aligned with findings by Kasperska-Zajac et al. [5].

A study by Takahagi et al. [6] revealed that many markers of inflammation and blood coagulation are essential in evaluation of disease severity and activity in chronic urticaria.

IL-6 levels were significantly higher in CSU patients when compared to the controls (9.1 ± 5.1 vs. 3.12 ± 2.8 pg/mL, p = 0.004), correlating strongly with disease severity. This finding aligned with research by Fujii et al. [7] and Atwa et al. [8], who proposed IL-6 as a potential biomarker for CSU severity. Total IgE levels were significantly elevated in patients (212.6 ± 239.8 vs. 67.8 ± 72.3 IU/mL, p < 0.001), consistently with research by Kessel et al. [9], suggesting its potential role in disease pathogenesis and utility as a biomarker for disease severity. Multiple studies have recognized potential biomarkers associated with different types of chronic urticarias and have also established a significant correlation with disease progression [10–14].

In autoimmune urticaria, thorough investigational studies have shed light on the pathogenic mechanisms underlying this condition. Autoantibodies targeting specific entities of the skin have been observed in patients with autoimmune urticaria. These autoantibodies serve as essential biomarkers, provide insight into the pathogenesis of the disease, and pave the way for novel therapeutic targets [15–20].

CONCLUSION

This comprehensive study provided significant insights into the immunological profile of chronic spontaneous urticaria and its relationship with disease severity.

CSU patients showed distinct alterations in various immunological markers, with significantly elevated levels of IL-6 exhibiting a particularly strong correlation with disease activity and severity. The significant elevation of total IgE levels and its strong correlation with disease severity supported the involvement of IgE-mediated mechanisms in CSU pathogenesis. While anti-TPO antibodies were elevated, the lack of statistical significance suggested that thyroid autoimmunity may play a variable role in different patient populations.

These findings collectively enhance our understanding of CSU pathophysiology and suggest potential therapeutic targets, supporting the utility of monitoring immunological markers, particularly IL-6 and total IgE as objective measures of disease activity.

Based on the existing literature and our findings, we believe that our work and that of others in the domain lay the groundwork for future research on this aspect.

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