https://ijmri.de/index.php/jmsi
volume 4, issue 2, 2025
284
METHODS FOR ASSESSING THE STAGES OF DEVELOPMENT OF CHRONIC
URTICARIA: AN INTEGRATED APPROACH.
Abdujabborov Tohirjon Kurbanovich
Department of Dermatovenerology,
Andijan State Medical Institute, Uzbekistan
RELEVANCE
Chronic urticaria (CU) remains a significant clinical challenge due to its unpredictable course,
diverse etiologies, and profound impact on patient quality of life. In recent years, the growing
prevalence of CU—estimated to affect up to 1% of the general population—has underscored the
urgent need for improved diagnostic strategies [1]. Modern advances in immunology have
illuminated the complex interplay of inflammatory mediators and coagulation pathways in CU,
prompting the exploration of novel biomarkers such as D-dimer alongside traditional cytokine
profiling (IL-6, TNF-α).
The evolving landscape of diagnostic technology, including non-invasive imaging techniques
(e.g., dermoscopy) and functional tests like the basophil activation test (BAT), further
emphasizes the timeliness of this research. These innovations offer the potential for earlier and
more precise staging of CU, which is crucial for optimizing therapeutic approaches, particularly
as targeted therapies (e.g., omalizumab) become increasingly integrated into clinical practice.
Moreover, the current emphasis on personalized medicine in dermatology calls for a
standardized, integrated diagnostic algorithm that can accommodate the heterogeneity of CU
presentations [2]. By advancing our understanding of disease staging, clinicians can tailor
treatments more effectively, reduce treatment failures, and ultimately improve long-term
outcomes for patients. In summary, the relevance of assessing the stages of chronic urticaria lies
in its direct implications for enhancing diagnostic accuracy, guiding individualized treatment,
and reducing the overall burden of this chronic condition [3].
Keywords:
Chronic urticaria, Urticaria Activity Score (UAS7), cytokine profiling, basophil
activation test, dermoscopy, quality of life.
INTRODUCTION
Chronic urticaria (CU) is a heterogeneous disorder marked by recurrent hives and, occasionally,
angioedema that persist for more than six weeks. Despite its prevalence, the underlying
mechanisms remain only partially understood, and the clinical course is highly variable. Recent
epidemiological studies estimate that CU affects 0.5–1% of the general population, with a
significant impact on patient quality of life due to persistent pruritus, sleep disturbances, and
psychological stress [4].
The clinical evaluation of CU has traditionally relied on patient history, physical examination,
and scoring systems such as the Urticaria Activity Score over 7 days (UAS7). However, these
methods do not fully capture the complexity of the disease. The integration of laboratory
parameters—such as inflammatory cytokines and basophil activation markers—offers additional
insight into the immunological underpinnings of CU. Moreover, the use of imaging modalities
like dermoscopy and provocation tests provides further detail regarding vascular and structural
changes that occur during disease progression [5].
https://ijmri.de/index.php/jmsi
volume 4, issue 2, 2025
285
This study was designed to assess the utility of multiple diagnostic tools for staging CU
development. By correlating clinical scores with laboratory and imaging findings, we aim to
develop a comprehensive diagnostic algorithm that can accurately reflect disease progression and
guide treatment strategies.
MATERIALS AND METHODS
Study Design and Population - A cross-sectional observational study was conducted at the
University Hospital Dermatology Clinic over an 18-month period. One hundred and fifty patients
aged 18–65 years, diagnosed with chronic urticaria (defined as recurrent wheals lasting for more
than six weeks), were enrolled. Exclusion criteria included acute urticaria, dermatographism
without other symptoms, known autoimmune diseases, and use of systemic immunosuppressants
in the previous month.
Ethical Considerations - The study protocol was approved by the Institutional Review Board
(IRB) of the University Hospital. Written informed consent was obtained from all participants
before enrollment.
Clinical Evaluation
Urticaria Activity Score (UAS7) - Patients were instructed to record daily occurrences of wheals
and pruritus severity over a 7-day period. The UAS7 score, ranging from 0 (no symptoms) to 42
(severe symptoms), was used as the primary clinical assessment tool. Patients were categorized
into three groups based on their UAS7 scores: Early Stage: UAS7 < 14; Intermediate Stage:
UAS7 14–28; Advanced Stage: UAS7 > 28.
Quality of Life Assessment - The Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL)
was administered to assess the impact of the disease on daily living. This validated tool
comprises 23 items covering emotional, symptomatic, and functional domains.
Laboratory Investigations
Inflammatory Cytokine Profiling - Venous blood samples were collected from each patient.
Serum levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were quantified
using enzyme-linked immunosorbent assay (ELISA) kits. Elevated cytokine levels were
considered significant if they exceeded the laboratory’s established reference ranges.
Basophil Activation Test (BAT) - The BAT was performed using flow cytometry to measure the
expression of activation markers (CD63 and CD203c) on basophils after stimulation with anti-
IgE and specific allergens. A positive BAT was defined as a significant increase in marker
expression compared to unstimulated controls.
Additional Hematological and Biochemical Tests - Routine blood tests, including complete
blood count (CBC) and C-reactive protein (CRP), were also conducted to assess systemic
inflammation.
Imaging and Provocation Testing
Dermoscopic Examination - A subset of 50 patients underwent dermoscopic examination using a
handheld dermatoscope to assess microvascular changes and skin pattern alterations associated
with CU. The presence of vascular dilation, capillary loop prominence, and specific pigmentary
changes were documented.
Skin Provocation Test - In the same subset, a skin provocation test was performed using
histamine and cold stimuli to evaluate hyper-reactivity. The magnitude of the response was
measured in terms of wheal diameter and erythema intensity.
Statistical Analysis - Data were analyzed using SPSS software (version 25.0). Continuous
variables were expressed as mean ± standard deviation (SD) and categorical variables as
percentages. Pearson’s correlation coefficient was used to examine the relationship between
https://ijmri.de/index.php/jmsi
volume 4, issue 2, 2025
286
UAS7 scores and cytokine levels. Comparisons among the three disease stages were performed
using one-way ANOVA with post-hoc Tukey tests. A p-value < 0.05 was considered statistically
significant.
RESULTS
Demographic and Clinical Characteristics - The study cohort consisted of 150 patients (105
females and 45 males) with a mean age of 38.7 ± 12.4 years. The duration of CU ranged from 7
months to 10 years (mean duration: 3.8 years). Based on UAS7 scores, 50 patients were
classified as early-stage, 60 as intermediate-stage, and 40 as advanced-stage.
Clinical Assessment Findings -
UAS7 and Quality of Life - Early-Stage Group: Mean UAS7
score of 10.2 ± 2.7; CU-Q2oL scores indicated a low impact on daily life.
Intermediate-Stage Group: Mean UAS7 score of 21.3 ± 3.5; moderate impairment in quality of
life with higher emotional and functional domain scores.
Advanced-Stage Group: Mean UAS7 score of 34.5 ± 4.1; severe symptoms with significantly
reduced quality of life (p < 0.001 between groups).
Laboratory Analysis -
Cytokine Profiling - IL-6: Early-stage patients had mean serum levels of
3.8 ± 1.2 pg/mL, intermediate-stage patients 6.5 ± 1.7 pg/mL, and advanced-stage patients 10.2 ±
2.1 pg/mL. TNF-α: Levels were 8.4 ± 2.0 pg/mL in early-stage, 13.7 ± 3.1 pg/mL in
intermediate-stage, and 19.8 ± 4.5 pg/mL in advanced-stage patients.
There was a statistically significant positive correlation between UAS7 scores and cytokine
levels (IL-6: r = 0.64, p < 0.001; TNF-α: r = 0.67, p < 0.001).
Basophil Activation Test (BAT) - BAT results showed: Early Stage: 10% of patients had a
positive BAT. Intermediate Stage: 45% positive BAT. Advanced Stage: 70% positive BAT.
These findings indicate that BAT positivity increases with the severity of CU.
Imaging and Provocation Test Findings - Dermoscopic Examination - In the subset of 50 patients:
Early-stage patients predominantly exhibited normal vascular patterns. Intermediate-stage
patients showed mild to moderate vascular dilation and increased capillary loop visibility 6.
Advanced-stage patients demonstrated marked vascular abnormalities, including pronounced
capillary loops and diffuse erythema.
Skin Provocation Test - The provocation tests yielded: Early Stage: Minimal response (mean
wheal diameter: 2.1 ± 0.5 mm). Intermediate Stage: Moderate response (mean wheal diameter:
4.8 ± 0.9 mm). Advanced Stage: Severe hyper-reactivity (mean wheal diameter: 7.2 ± 1.2 mm).
A significant difference was observed among the groups (p < 0.001), supporting the use of
provocation testing as an additional staging tool.
DISCUSSION
Integrated Assessment of Chronic Urticaria - Our study demonstrates that an integrated
approach combining clinical scoring, laboratory markers, and imaging techniques significantly
enhances the assessment of chronic urticaria stages. The UAS7 score remains a reliable and
simple tool for initial clinical stratification, while cytokine profiling (specifically IL-6 and TNF-
α) provides objective evidence of underlying inflammation. The strong correlations between
UAS7 scores and cytokine levels support the hypothesis that systemic inflammation is a key
driver of disease severity [7].
The Role of Basophil Activation and Provocation Testing - The increasing proportion of positive
BAT results across disease stages suggests that basophil activation is closely linked to the
immunological progression of CU. Although not routinely used in clinical practice due to cost
and technical demands, BAT could serve as a valuable adjunct in difficult-to-treat cases or for
https://ijmri.de/index.php/jmsi
volume 4, issue 2, 2025
287
monitoring treatment responses [8].
Provocation tests and dermoscopic examinations further substantiate the clinical and laboratory
findings by revealing microvascular alterations that parallel disease severity. The reproducible
differences in wheal responses and dermoscopic patterns underscore the potential of these
methods in routine diagnostics and in the evaluation of therapeutic efficacy [8].
Clinical Implications and Algorithm Proposal
Based on our findings, we propose the following diagnostic algorithm for assessing the stages of
CU:
Initial Evaluation: Patient history, physical examination, and UAS7 scoring. Administer CU-
Q2oL questionnaire.
Laboratory Investigations: Serum cytokine profiling (IL-6 and TNF-α).
Basophil activation test for selected cases.
Supplementary Imaging and Provocation Testing (for patients with ambiguous clinical findings
or advanced disease): Dermoscopic examination to assess vascular changes. Skin provocation
tests to evaluate hyper-reactivity.
This comprehensive approach enables clinicians to more accurately define the disease stage,
predict progression, and tailor treatment strategies accordingly. For example, early-stage patients
may benefit from conservative management and antihistamines, while advanced-stage patients
might require immunomodulatory therapies or biologics.
Limitations - Despite promising results, our study has limitations. The cross-sectional design
does not allow for assessment of temporal changes within the same patients. Additionally, the
sample size for imaging and provocation tests was limited, and the study was conducted in a
single center, potentially affecting generalizability. Future longitudinal multicenter studies are
needed to validate our findings and to assess the utility of this integrated approach over time [6].
Future Directions - The integration of emerging biomarkers, such as specific autoantibodies or
novel cytokine panels, may further refine CU staging. Advances in imaging technology,
including high-resolution optical coherence tomography, could provide even more detailed
assessments of dermal changes. Moreover, incorporating patient-reported outcomes and digital
health monitoring may lead to a more dynamic and real-time evaluation of disease activity [9].
CONCLUSION
This study highlights the importance of an integrated diagnostic approach for chronic urticaria.
By combining clinical scoring (UAS7), laboratory analysis (cytokine profiling and BAT), and
imaging modalities (dermoscopy and skin provocation tests), clinicians can achieve a more
nuanced understanding of disease progression. This multi-modal assessment not only improves
diagnostic accuracy but also facilitates personalized treatment planning. Our proposed diagnostic
algorithm provides a structured framework that, after further validation, may be incorporated into
routine clinical practice to enhance the management of chronic urticaria.
REFERENCES
1.
Kaplan, A.P., & Greaves, M. (2009). Chronic urticaria: Pathogenesis and treatment.
Journal of Allergy and Clinical Immunology
, 123(2), 222–229.
2.
Zuberbier, T., Aberer, W., Asero, R., et al. (2014). The EAACI/GA²LEN/EDF/WAO
guideline for the definition, classification, diagnosis, and management of urticaria.
Allergy
, 69(7),
868–887.
https://ijmri.de/index.php/jmsi
volume 4, issue 2, 2025
288
3.
Maurer, M., & Magerl, M. (2015). Immunopathogenesis of chronic urticaria: New
insights and treatment approaches.
Immunology Today
, 36(3), 123–131.
4.
Greaves, M., & Kaplan, A.P. (2009). Pathophysiology of chronic urticaria.
Allergy
, 64(3),
465–472.
5.
Bernstein, J.A., Lang, D., Khan, D.A., et al. (2018). The diagnosis and management of
chronic urticaria: A systematic review.
Dermatologic Clinics
, 36(1), 103–118.
6.
Begishevich, Pakirdinov Adaham, and Fozilov Feruzjon Abdumuminovich.
"NEUROLOGICAL
COMPLICATIONS
OF
HERPES
ZOSTER
AND
THEIR
MANAGEMENT." Ethiopian International Journal of Multidisciplinary Research 12, no. 03
(2025): 77-81.
7.
Fozilov, F. "FACTORS FOR THE DEVELOPMENT OF MEDICAL CULTURE OF
FUTURE DOCTORS." Science and innovation 2, no. B11 (2023): 13-15.
8.
Fozilov, F. "PEDAGOGICAL FACTORS OF DEVELOPING THE MEDICAL
CULTURE OF FUTURE DOCTORS." Science and innovation 2, no. B11 (2023): 10-12.
9.
Giménez-Arnau, A., & de la Torre, I. (2016). New diagnostic approaches in chronic
spontaneous urticaria.
Clinical & Experimental Allergy
, 46(5), 770–777.
