Assessment of serum total immunoglobulin E levels as a biomarker of severity and duration of chronic spontaneous urticaria: A cross-sectional study

INTRODUCTION

Urticaria is an inflammatory disorder presenting with transient wheals, angioedema, or both, without systemic symptoms. It occurs as a consequence of the degranulation of mast cells, which can be spontaneous or triggered by various agents. Acute urticaria (duration <6 weeks) is often associated with infections or food, or drugs. Chronic urticaria (CU) (duration >6 weeks) may be spontaneous (chronic spontaneous urticarial [CSU]) when no specific trigger can be found, associated with systemic disorders, or inducible (chronic inducible urticaria, CIndU) by well-defined stimuli.^[1] Urticaria affects a significant proportion of the population, with a reported prevalence ranging from 0.5% to 1.8%. It can occur at any age, but it is more commonly observed in adults. Women are more frequently affected than men, with a female-to-male ratio of approximately 2:1. The condition can persist for months or even years, causing chronic discomfort and distress for patients.^[2]

In addition, the hallmark symptom of urticaria is the appearance of wheals or hives on the skin. These wheals are usually raised, red or pink, and intensely itchy. They can vary in size and shape, often changing their location within a few hours. The wheals may occur on any part of the body, including the face, trunk, extremities, and mucous membranes.^[3,4]

The exact etiology of CU is often complex and multifactorial, involving a combination of immunological, genetic, and environmental factors. In a significant proportion of cases, the cause remains unknown and is classified as idiopathic CU. However, several known triggers and risk factors have been identified, including autoimmune factors; infections, particularly viral or bacterial infections; physical stimuli; certain medications such as non-steroidal anti-inflammatory drugs, antibiotics, and angiotensin-converting enzyme inhibitors; and psychological factors such as emotional stress and anxiety.^[5]

Urticaria is a common disease, but its underlying pathogenesis is not well understood. The pathogenesis of urticaria is probably due to vasodilation that causes increased vascular permeability and release of vasoactive substances by mast cells in the skin. Mast cells contain granules with preformed mediators such as histamine, cytokines, and chemokines, which are released before the production of other inflammatory molecules. These mediators can attract eosinophils, neutrophils, and T cells to the affected area. The skin of individuals with urticaria also shows an infiltration of monocytes, basophils, and CD4+ T cells. Cytokines associated with Th2 immune response, such as interleukin (IL)-33, IL-25, IL-4, and IL-5, are present in the affected skin.^[6,7]

Immunoglobulin E (IgE) is an antibody produced by the immune system, in which elevated IgE levels are commonly observed in allergic conditions, including acute urticaria, yet the role of IgE in CU is unclear. In CU, the presence of autoantibodies targeting IgE receptors on mast cells and basophils is thought to play a more significant role in disease pathogenesis than the total IgE levels.^[8,9]

However, it is noteworthy that some patients with CU may have elevated IgE levels, particularly in cases associated with allergic triggers or atopic conditions. Although serum IgE levels are often elevated in patients with atopic dermatitis (AD), they do not consistently reflect the clinical severity of the skin disease. This means that patients with mild AD may have very high IgE levels, while others with severe disease may have only modest elevations or even normal levels. Therefore, IgE is not a reliable biomarker for monitoring disease severity. However, measuring total and specific IgE can still provide useful information regarding a patient’s overall atopic status, such as sensitization to environmental or food allergens, which may help identify potential triggers and guide allergen avoidance strategies or adjunctive therapies.^[8]

MATERIAL AND METHODS

This was a cross-sectional study that included 97 patients suffering from CSU who were referred to the CU and immunology unit of Cairo Hospital of Dermatology and Venereology (Al-Haud Al-Marsoud) from March 2024 to December 2024. All the study patients were investigated for total serum IgE levels. The study was approved by the Training and Research Sector in the Egyptian Ministry of Health and Population (Ethical Committee No: 2–2024/13). Informed written consents were obtained from the patients before enrollment in this study.

Inclusion criteria were adults aged 20–50 years, of both sexes, diagnosed with CSU, whereas exclusion criteria were pregnant or lactating women and individuals with a history of malignancies or with AD.

RESULTS

The mean age was 31.6 ± 8.4 years. There were 37 (38.1%) males and 60 (61.9%) females. The CSU disease total severity score ranged between 6 and 18, with a mean score of 9.6, including 30 patients (30.9%) with mild severity, 43 patients (44.3%) with moderate severity, and 24 patients (24.7%) with severe disease. The total serum IgE levels ranged between 32 and 942 IU/mL, with a mean score of 200 IU/mL and a median of 154 IU/mL, including 49 patients (49.5%) with high levels (>150 IU/mL) [Table 2].

About half of the patients reported the number of lesions to be ≤10, while more than half of the patients had wheals <1 cm in diameter. Severe pruritus was reported by 37.1%, while almost 59% of patients had lesions that lasted <1 hour. Around two-thirds of patients had lesions once a week, while the daily dose of antihistamines was reported by 56.7% of patients [Table 3].

Table 4 demonstrates the association between IgE levels and disease duration and disease severity. The mean disease duration was significantly higher in patients with high IgE levels (26.3 months), compared to patients with normal IgE levels (17.9 months, P < 0.001). Similarly, the mean CU severity score was significantly higher in patients with high IgE levels (11.1 IU/mL), compared to patients with normal IgE levels (6.4 IU/mL, P < 0.001). Table 5 demonstrates the association between disease severity and disease duration. The mean disease duration differed significantly in mild (11.8 months), moderate (23.3 months), and severe disease (33.2 months, P < 0.001). Post hoc tests showed significant differences in all pair comparisons (P < 0.001). There were significant positive correlations between total serum IgE levels and disease severity (r = 0.663) and disease duration (r = 0.518). Further, there was a significant positive correlation between disease severity and disease duration (r = 0.761) [Table 6]. A significant positive correlation between IgE levels (normal and high) and disease severity levels (mild, moderate, and severe) was also obtained [Table 7], whereas there was no statistically significant correlation between the total serum IgE levels and the age and sex of the patients.

DISCUSSION

CSU is a prevalent allergic dermatologic condition characterized by the spontaneous emergence of pruritic wheals (hives), angioedema, or both, persisting for more than 6 weeks. The pathophysiology of CSU is thought to involve autoimmune mechanisms, particularly the presence of autoantibodies targeting IgE or its high-affinity receptors on mast cells and basophils, leading to histamine release. This study aimed to evaluate serum total IgE levels in patients with CU and examine their relationship with disease severity. An epidemiological study by Wang et al. (2022),^[11] that encompassed 12 hospitals and included 1,715 outpatients (198 with autoimmune urticaria and 1,517 with CU), reported a female predominance among patients older than 20 years. This gender disparity is likely attributable to the modulatory effects of female sex hormones on immune responses, particularly given the higher prevalence of autoimmune diseases in women. Mast cells, which play a central role in CSU pathogenesis, express hormone receptors and may be activated or sensitized under the influence of estrogen and other sex hormones, thereby amplifying the inflammatory response.^[11]

In the present study, the disease duration among enrolled patients ranged from 2 to 48 months, with a mean duration of 22.1 months. Nearly half of the participants (n = 47, 48.5%) presented with fewer than 10 wheals, which aligns with findings from an Egyptian cohort reported by Shebiny et al.,^[12] where 40.5% of patients exhibited fewer than 10 lesions. However, Dias et al.^[13] emphasized that wheal count and pruritus intensity alone may be insufficient to comprehensively assess disease activity or monitor therapeutic response in CSU.^[12,13]

Elevated serum total IgE levels were observed in 50.5% of patients in our study, with values ranging from 32 to 942 IU/mL (mean: 200 IU/mL; median: 154 IU/mL). Notably, 49.5% of patients had IgE levels exceeding 150 IU/mL. These findings are consistent with prior studies by Altrichter et al. and Gao et al.,^[8,14] both of whom reported elevated total IgE levels in approximately half of their respective CSU cohorts. These authors proposed that serum IgE may serve not only as a disease marker but also as a predictive biomarker for treatment response, particularly in relation to endotype differentiation and therapeutic targeting.^[8,14]

While previous studies have demonstrated a correlation between higher IgE levels and prolonged disease duration or increased severity, our data revealed slightly different trends. Elevated IgE levels were most frequently observed in patients with disease durations of 25–36 months (49%) and were less prevalent in those with disease durations exceeding 36 months (8.2%). Furthermore, a greater proportion of patients with moderate disease severity exhibited elevated IgE levels (55.1%) compared to those with severe disease (36.7%). These variations may reflect the smaller sample size of our cohort relative to those in the studies by Gao et al. ^[14] (302 patients) and Altrichter et al.^[8] (926 patients), limiting the generalizability of these specific findings.

Assessment of disease severity in our cohort, based on the CU total severity score (CUTSS), revealed 30.9% with mild disease, 44.3% with moderate disease, and 24.7% with severe presentations. The CUTSS is a multidimensional tool that evaluates the number and size of wheals, pruritus intensity, duration, and frequency of episodes, and antihistamine usage, with each component scored from 0 to 3, allowing a maximum score of 18.

In this study, total serum IgE levels demonstrated a significant positive correlation with both disease duration (r = 0.518, P < 0.001) and severity (r = 0.663, P < 0.001). Furthermore, disease duration and severity were themselves strongly correlated (r = 0.761, P < 0.001). These results are in agreement with the findings of Kessel et al., who also reported elevated IgE levels in patients with more severe and long-standing CSU.^[15]

CONCLUSION

CSU compromises patients’ quality of life, mainly those with more severe disease or who are diagnosed with chronic autoimmune urticaria. Increased serum-free IgE is involved in the development of CSU by activating mast cells. The link between IgE levels and CSU severity may be explained by the effect of IgE on mast cell activation and degranulation. Our findings of elevated IgE levels in CSU patients suggest that CSU could be regarded as an immune-mediated disorder. Finally, IgE levels should be considered to be used as a marker to evaluate CSU patients and assess disease severity as well as duration, thereby potentially affecting patient management.