For millions living with chronic hives, a common blood test may finally provide answers.
Imagine waking up daily with unpredictable, itchy welts that come and go without warning. For over 3 million Americans living with chronic spontaneous urticaria (CSU), this is their reality—a frustrating condition where hives appear spontaneously, often with no identifiable trigger. But recent research has uncovered an important clue in understanding this mysterious condition: elevated C-reactive protein (CRP) levels. This common marker of inflammation, found in a simple blood test, is providing new insights into why these hives occur and how to better treat them.
C-reactive protein is a substance produced by your liver in response to inflammation somewhere in your body. Think of it as your body's "inflammatory fire alarm"—when levels are elevated, it indicates that your immune system is activated, even if you can't feel it.
~33%
of CSU patients show elevated CRP levels, suggesting systemic inflammation plays a key role 1
CRP acts as your body's alert system for inflammation. When elevated, it signals that your immune system is actively fighting something—even if you can't see or feel the source.
In healthy individuals, CRP levels typically remain low. But in chronic inflammatory conditions, including chronic spontaneous urticaria, this marker can tell an important story about what's happening beneath the skin's surface.
Research has revealed that approximately one-third of CSU patients show elevated CRP levels, suggesting that systemic inflammation plays a key role in many cases 1 . This discovery has been groundbreaking in helping healthcare providers understand that chronic hives aren't just a superficial skin issue—for many patients, they're the visible sign of an underlying inflammatory process.
So why exactly are CRP levels elevated in chronic hives? The answer appears to lie in the autoimmune component of the condition.
Studies have found that CRP levels are significantly higher in patients with a positive autologous serum skin test (ASST)—a marker of autoimmune activity in urticaria 2 .
One study comparing 194 CSU patients with healthy controls found significant differences in CRP levels based on autoimmune activity 2 .
This autoimmune connection helps explain why chronic hives can be so persistent and difficult to treat. In autoimmune CSU, the body produces antibodies that chronically activate mast cells—the immune cells in skin tissue responsible for hive formation. This constant activation creates a state of low-grade inflammation throughout the body, reflected by those elevated CRP levels.
In 2018, a significant study published in the journal Allergy examined the relationship between CRP and chronic spontaneous urticaria in 1,253 patients across two medical centers 1 . This large-scale research provided some of the most compelling evidence to date about the importance of CRP in understanding and treating chronic hives.
The researchers took a comprehensive approach to understanding CRP's role in CSU:
Serum CRP levels were measured using the nephelometric method, a precise way to quantify this inflammatory marker.
Researchers collected extensive data including urticaria activity scores, quality of life measures, and response to antihistamine treatment.
The study also examined other inflammatory and coagulation markers including ESR, D-dimer, fibrinogen, and complement levels 1 .
For most patients, researchers gathered information on demographics, disease duration, presence of angioedema, comorbidities, and ASST results 1 .
The results of this extensive study revealed several important connections between CRP and chronic hives:
CRP levels showed a significant correlation with urticaria activity scores, meaning that as hive severity increased, so did CRP levels 1 .
Perhaps one of the most clinically valuable findings—CRP levels were significantly higher in patients who didn't respond well to standard antihistamine treatment compared to those who did 1 .
Elevated CRP also correlated with greater impairment in quality of life measures, reflecting the broader impact of this inflammatory state 1 .
CRP levels correlated with other markers of inflammation and coagulation, suggesting CRP is part of a larger inflammatory picture in CSU 1 .
| CRP Level | Prevalence in CSU | Associated Features | Treatment Implications |
|---|---|---|---|
| Normal | ~67% of patients | Better response to antihistamines | May respond well to standard therapies |
| Elevated | ~33% of patients | Higher disease activity, autoimmune features, poorer quality of life | May require earlier escalation to advanced therapies |
The practical value of CRP testing in chronic hives extends far beyond mere diagnosis—it's increasingly useful in guiding treatment decisions and predicting responses to therapy.
Research indicates that patients with elevated CRP levels tend to be less responsive to standard doses of antihistamines, the first-line treatment for CSU 1 . This knowledge can help healthcare providers develop more personalized treatment plans, potentially moving more quickly to advanced therapies for these patients.
Similarly, emerging evidence suggests that CRP levels and other inflammatory markers may help predict response to omalizumab, a biologic medication used for treatment-resistant chronic hives 6 . Patients with elevated inflammatory markers may show different response patterns to this targeted therapy.
| Treatment Type | Response with Normal CRP | Response with Elevated CRP |
|---|---|---|
| Antihistamines | Better response | Often reduced effectiveness |
| Omalizumab | Variable | May require different dosing or earlier escalation |
| Cyclosporine | Limited data | May be particularly beneficial for autoimmune profile |
CRP doesn't work in isolation—it's part of a complex network of inflammatory markers that become activated in chronic spontaneous urticaria.
A 2023 study discovered that elevated CRP levels in CSU correlate with increased expression of miR-221, a specific microRNA linked to inflammation and autoimmunity 5 .
The same study found that high CRP and miR-221 levels were associated with elevated IL-31, a cytokine known as the "itch cytokine" 5 .
CRP often elevates alongside other inflammation indicators like ESR and IL-6, creating a more complete picture of the inflammatory state in CSU 7 .
| Marker | Role in Inflammation | Significance in CSU |
|---|---|---|
| CRP | Acute phase protein, general marker of inflammation | Correlates with disease activity, treatment response |
| ESR | Measures how quickly red blood cells settle in a tube | Correlates with disease severity, may indicate inflammatory activity |
| IL-6 | Cytokine that stimulates immune response | Linked to daily symptom severity and quality of life impact |
| D-dimer | Marker of fibrin breakdown, indicates coagulation activation | Associated with more severe, difficult-to-control disease |
"The recognition of CRP's role in chronic hives comes at a promising time. The treatment landscape for CSU is rapidly evolving, with new therapies offering hope for patients who haven't responded to traditional treatments."