Sir,
Acute urticaria (AU) is a spontaneous mast-cell-driven cutaneous disease accompanied by release of histamine and other cytokines from active mast cells, with occurrence of wheals and/or angioedema and other systemic symptoms of <6 weeks duration. Bacterial infection was considered as one of the causative factors in AU. Procalcitonin (PCT) and interleukin-6 (IL-6) are important biomarkers in the diagnosis or prognosis of bacterial diseases.[1,2] Our previous study has demonstrated that PCT and IL-6 are critical inflammation markers in the evaluation of bacteria-induced dermatosis.[3] In AU, there are evidences that laryngeal angioedema, acute intestinal, and stomach swelling are medical emergencies requiring prompt assessment and a period of symptomatic therapy. It has always been a challenge to ascertain the pathogenesis during the early disease onset, and plenty of causative factors including the potential allergic exposure, recent infection, history of concurrent medications, and ingestion of foods can induce AU. Data concerned on multiple inflammatory biomarkers in AU are limited. Thereby, we facilely performed combinatorial assessments of serum reactants and immunoglobulin E (IgE) to explore the potential etiology in AU patients with systemic symptoms.
All patients were diagnosed as AU following the EAACI/GA2 LEN/EDF/WAO guideline.[4] After obtaining informed consent, 42 adults and 23 children were enrolled to meet at least two or more of the following clinical presentations (generalized lesions, fever [>38°C], laryngeal angioedema, chest tightness, and abdominal pain) in our study from June to September, 2015. Patients received systemic therapies including anti-histamine, glucocorticoid, and/or antibiotic when necessary for 5–7 days. Data were presented as median (25-75% percentiles). Differences between two variables were analyzed by Mann–Whitney U-test. P < 0.05 was considered significant.
As demonstrated in Table 1, in both adult and child groups, there were significant elevations of serum D-dimer, PCT, IL-6, C-reactive protein (CRP), and white blood cell count (WBC) levels in the early stage group, with the median value of at least 140% (WBC) and up to about 20-fold change (CRP) of their maximum laboratory reference values. The values of these markers decreased remarkably after treatment. Furthermore, there were significant differences of these biomarkers between fever group and nonfever group during the early stage. These results indicate that D-dimer, PCT, IL-6, CRP, and WBC can be used as crucial biomarkers to monitor the disease severity and activity of AU with systemic symptoms. Whereas, IgE and anti-streptolysin O levels did not differ before and after the treatment as well as between fever and nonfever group, indicating that IgE-mediated allergy and streptococcal infection are less likely to cause the urticaria lesion in this study. Normally, traditional markers of CRP and WBC are not specific for indication of bacterial infections. PCT below 0.1 ng/mL signifies the endpoint of bacterial infection that determines the discontinuation of antibiotic therapy.[5] Consequently, PCT levels help guide the antibiotic administration in our work. Sustained low serum levels of IL-6 have been shown to predict effective therapy.[2] Elevated D-dimer levels suggest that a tissue factor pathway would lead to the activation of coagulation. This combinatorial and comparable study of these serum reactants allows clinicians to monitor the clinical outcome and guide the antibiotic management in AU patients.
Table 1.
Values of serum D-dimer, procalcitonin, interleukin-6, C-reactive protein, anti-streptolysin O, white blood cell count and total immunoglobulin E in patients with acute urticaria accompanied by systemic symptoms
| Group | Adult (n=42) | |||
|---|---|---|---|---|
| Characteristics | Fever, n=22, m=10, f=12; Age, 27 year (20.75-37.25) | Nonfever, n=20, m=10, f=10; Age, 31.5 year (28.25-46) | ||
| Biomarkers | Early stage | Remission | Early stage | Remission |
| D-dimer (μg/mL) | 3.68 (1.00-9.50)*,# | 0.74 (0.56-1.01) | 1.81 (0.58-3.84)* | 0.72 (0.46-1.01) |
| PCT (ng/L) | 0.14 (0.06-0.18)*,# | 0.04 (0.03-0.05) | 0.06 (0.03-0.09)* | 0.03 (0.03-0.05) |
| IL-6 (pg/L) | 43.40 (13.91-138.20)*,# | 6.51 (3.78-14.34) | 16.66 (2.85-49.20)* | 4.72 (2.56-6.64) |
| CRP (mg/L) | 62.36 (21.31-105.42)*,# | 8.55 (3.31-11.51) | 25.20 (4.31-67.84)* | 3.70 (2.24-10.56) |
| ASO (IU/mL) | 60.00 (40.00-142.75) | 66.50 (36.50-152.25) | 50.50 (32.75-110.50) | 45.50 (21.50-109.75) |
| WBC (×109/L) | 13.64 (9.89-16.80)*,# | 8.67 (7.27-11.14) | 10.39 (8.59-13.26)* | 8.60 (6.81-10.86) |
| IgE (IU/ml) | 57.00 (33.50-78.50) | 64.50 (44.00-89.50) | 67.00 (23.00-225.25) | 67.50 (29.00-230.75) |
| Group | Child (n=23) | |||
| Characteristics | Fever (n=13, m=6, f=7); Age, 6.00 year (3.50-10.00) | Nonfever (n=10, m=5, f=5); Age, 6.00 year (3.00–8.25) | ||
| Biomarkers | Early stage | Remission | Early stage | Remission |
| D-dimer (μg/mL) | 4.64 (1.61-9.51)*,# | 0.82 (0.58-2.03) | 1.42 (0.62-3.05)* | 0.73 (0.42-1.12) |
| PCT (ng/L) | 0.25 (0.14-0.66)*,# | 0.05 (0.05-0.06) | 0.09 (0.07-0.17)* | 0.05 (0.04-0.05) |
| IL-6 (pg/L) | 42.83 (26.15-110.65)*,# | 7.46 (6.21-29.29) | 18.55 (8.48-33.89)* | 6.22 (4.61-11.11) |
| CRP (mg/L) | 26.43 (13.64-90.31)*,# | 7.32 (2.75-9.44) | 13.64 (6.25-18.46)* | 2.57 (2.13-3.93) |
| ASO (IU/mL) | 41.00 (2.00-106.00) | 51.00 (3.50-94.00) | 44.00 (2.00-62.75) | 46.00 (3.00-58.00) |
| WBC (×109/L) | 14.04 (10.19–18.29)*,# | 9.48 (7.14–12.33) | 10.44 (8.15–14.89)* | 7.27 (6.89–9.97) |
| IgE (IU/ml) | 58.00 (22.50–257.50) | 48.00 (22.50–265.00) | 70.50 (32.75–105.50) | 81.50 (39.00–91.25) |
*Significant difference to remission group, #Significant difference to nonfever group in early stage. PCT: Procalcitonin, IL-6: Interleukin-6, CRP: C-reactive protein, ASO: Anti-streptolysin O, WBC: White blood cell count, IgE: Immunoglobulin E
Financial support and sponsorship
The fund for youth of the First Affiliated Hospital of Anhui Medical University (2013KJ17, 2013KJ18).
Conflicts of interest
There are no conflicts of interest.
Acknowledgment
This research was supported by the fund for youth of the First Affiliated Hospital of Anhui Medical University (2013KJ17, 2013KJ18). We thank Professor Pei Guang Wang for many helpful discussions.
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