Biomarkers in Childhood Chronic Spontaneous Urticaria
For the parents of the nearly 1 in every 100 children affected by Chronic Spontaneous Urticaria, life becomes a frustrating cycle of itchy welts, sleepless nights, and endless questions with few answers.
Imagine seeing your child covered in itchy, red welts day after day, with no clear trigger and no end in sight. This is the reality for families dealing with Chronic Spontaneous Urticaria (CSU) in children, a mysterious skin condition where hives appear spontaneously for more than six weeks. Unlike allergic reactions, these hives seem to have no cause, making them incredibly difficult to predict, manage, and treat. For decades, doctors and researchers have searched for objective ways to measure what's happening inside a child's body during this distressing condition. The answer may lie in biomarkers - measurable biological clues that can reveal the severity of the disease and guide more effective, personalized treatment.
Chronic Spontaneous Urticaria is more than just an occasional rash. It's a complex mast cell-driven disease characterized by the sudden appearance of wheals (hives) and/or angioedema (deep tissue swelling) that persists for over six weeks without an identifiable trigger 5 .
While about 1% of the general population lives with CSU, its impact on children is particularly profound. The condition can disrupt sleep, impair concentration at school, lead to social anxiety, and significantly reduce a child's quality of life. The "spontaneous" nature of the outbreaks—their unpredictable coming and going—adds a layer of psychological stress for both children and their parents.
The central players in CSU are mast cells, a type of immune cell residing in the skin. When activated, these cells release a cocktail of inflammatory mediators, most notably histamine, which causes itching, redness, and swelling. However, the fundamental question of what triggers this activation in CSU has puzzled scientists for years, leading to the search for biomarkers that can unravel this mystery 5 .
1%
of general population affected by CSU
>6 weeks
for CSU diagnosis
In simple terms, biomarkers are measurable biological indicators that provide information about a disease state. Think of them as molecular fingerprints that a disease leaves behind, offering clues about its severity, activity, and potential response to treatment.
In the context of CSU, researchers are investigating various types of biomarkers:
These biomarkers aren't just abstract scientific concepts; they represent real pathways and processes active in a child's body during CSU flares. By learning to read these clues, doctors hope to move beyond simply treating symptoms to addressing the underlying drivers of the disease.
While most biomarker research has focused on adults, a groundbreaking 2025 study specifically investigated children with CSU, comparing 45 young patients to 39 healthy children of similar age and gender 1 .
The researchers recruited 84 children total—45 diagnosed with CSU and 39 healthy controls. This careful matching helped ensure that any differences found would likely relate to the disease itself rather than other factors.
Each child with CSU underwent standardized evaluation using two validated tools:
Researchers collected blood samples from all participants and used specialized laboratory techniques to measure serum periostin levels (SPL).
The team also analyzed whether children receiving different treatments (antihistamines alone versus antihistamines plus leukotriene receptor antagonists) showed different periostin levels.
Contrary to what some might expect, the research revealed that children with CSU had significantly lower serum periostin levels (56.41 ng/mL) compared to healthy children (71.68 ng/mL) 1 .
| Group | Number of Children | Mean Serum Periostin Level (ng/mL) |
|---|---|---|
| CSU Patients | 45 | 56.41 ± 20.32 |
| Healthy Children | 39 | 71.68 ± 20.36 |
| Parameter | Value | Interpretation |
|---|---|---|
| Area Under Curve (AUC) | 0.705 | Fair to good diagnostic accuracy |
| 95% Confidence Interval | 0.593-0.817 | Statistically significant |
| p-value | 0.001 | Highly significant |
Perhaps most intriguingly, the research discovered that children receiving more advanced treatment (leukotriene receptor antagonists plus antihistamines) showed significantly lower periostin levels than those on antihistamines alone (44.32 vs. 61.33 ng/mL) 1 . This suggests that periostin might reflect disease activity that responds to targeted treatment.
While the periostin study broke new ground, other biomarkers are also showing promise for understanding childhood CSU:
| Biomarker Category | Specific Biomarker | Association with CSU | Potential Clinical Utility |
|---|---|---|---|
| Novel Proteins | Serum Periostin | Lower in CSU children vs. controls 1 | Disease detection, treatment monitoring |
| MRGPRX2 | Higher in severe CSU 7 | Severity indicator | |
| Substance P | Higher in severe CSU 7 | Severity indicator | |
| Immune Cells | Eosinophils | Elevated in progressive disease 2 | Risk stratification |
| Basophils | Low counts indicate severe disease 8 | Severity assessment, treatment response | |
| Clinical Scores | UAS7 | Predicts transition to chronicity 2 | Early intervention guidance |
What does it take to study these biomarkers in children with CSU? Here's a look at the essential tools researchers use:
Enzyme-linked immunosorbent assay kits allow researchers to measure specific proteins like periostin, MRGPRX2, and Substance P in blood samples 7 .
These sophisticated instruments analyze immune cell populations and surface markers, helping count basophils and eosinophils.
Validated tools like UAS7 and UCT provide standardized disease activity measurements across different patients and studies 1 .
Proper facilities for storing serum samples at -80°C ensure biomarker stability for future analysis 7 .
The discovery of biomarkers in childhood CSU opens exciting possibilities for the future. Instead of the traditional trial-and-error approach to treatment, doctors may soon be able to:
Identifying which children with acute urticaria are likely to develop chronic forms.
Matching specific therapies to a child's unique biomarker profile.
Using biomarker changes to assess whether a treatment is working.
Avoiding treatments unlikely to benefit a particular child.
The journey to unravel the mysteries of childhood CSU is well underway. While biomarkers like periostin, eosinophils, and UAS7 scores are already providing valuable insights, the scientific community continues to search for more precise, reliable indicators. Each new discovery brings us closer to a future where every child with CSU can receive timely, effective, and personalized treatment—transforming this unpredictable condition from a source of daily frustration to a manageable part of life.
For researchers, clinicians, and families alike, these biological clues represent more than just laboratory values—they're beacons of hope, guiding the way toward better understanding and ultimately taming the mysterious rash that has baffled medicine for so long.