A letter to the editor in response to your published article in the Indian Journal of Skin Allergy

Dear Editor,

We sincerely thank the correspondents for their interest in our article entitled “Assessment of serum total immunoglobulin E (IgE) levels as a biomarker of severity and duration of chronic spontaneous urticarial (CSU): A cross-sectional study” published in the Indian Journal of Skin Allergy (2025;4:148–53).^[1] We highly appreciate their constructive comments and the opportunity to clarify the objectives and scope of our work.

The correspondents argue that our findings are limited by the absence of receiver operating characteristic (ROC) analysis, area under the ROC curve measurement, and cutoff value (CoV) determination. While we agree that ROC-derived CoVs are indispensable when the primary objective is diagnostic threshold setting or prognostic stratification,^[2,3] this was not the purpose of our study. Our cross-sectional work was designed to address a specific knowledge gap: Whether serum total IgE levels in Egyptian patients with CSU are consistently elevated and whether such elevations correlate with disease severity and duration. These questions were answered with statistical rigor, and the conclusions drawn remain robust and valid irrespective of ROC analysis. It is important to emphasize that biomarkers can serve multiple roles:

• Pathophysiological markers to elucidate disease mechanisms,

• Monitoring markers to reflect disease burden,

• Predictive markers to guide management.

Our study explicitly focused on the first two categories. By establishing a clear link between total IgE levels and both severity and chronicity of CSU, we laid the groundwork for IgE to be considered in disease monitoring. The correspondents’ insistence on CoV derivation overlooks the fact that CoVs are most meaningful in longitudinal or interventional designs, where biomarker thresholds can be validated against clinical outcomes such as remission, relapse, or treatment response. Attempting to calculate a CoV in a cross-sectional dataset such as ours risks spurious thresholds with little external validity.

We welcome the reviewer’s valuable remark that the absence of ROC analysis could be briefly acknowledged as a natural limitation inherent to the cross-sectional design. Accordingly, we emphasize that: “The lack of ROC analysis represents a natural methodological limitation inherent to cross-sectional studies, where predictive or temporal relationships cannot be established.”

Furthermore, no preliminary attempt was made to explore threshold behavior, as the dataset did not allow for statistically meaningful CoV estimation. The study’s aim was correlational, not predictive; therefore, defining a threshold without temporal validation would have risked misleading or non-generalizable results.We welcome the suggestion that future prospective, multicenter studies should aim to define reliable CoVs for IgE in CSU, ideally in combination with other promising biomarkers such as D-dimer, basophil activation markers, and interleukin-6.^[4-6] Such research will be invaluable in translating our pathophysiological findings into clinically actionable thresholds.

In conclusion, the primary objective of our study was never to establish CoVs for serum total IgE, and therefore, it should not be evaluated based on the absence of such an analysis. Our aim was to provide robust, population-specific data addressing whether IgE is consistently elevated in Egyptian patients with CSU, and whether such elevations correlate with disease severity and duration. By achieving this aim, our study offers novel evidence that strengthens the understanding of IgE as a potential biomarker in CSU. Rather than constituting a limitation, the clearly defined scope of our work ensures that the findings stand on firm methodological ground and represent a meaningful contribution to the literature. It is precisely this focus that makes our results valuable as a foundation for future longitudinal and interventional studies designed to establish clinically applicable thresholds.