European Journal of Cardiovascular Medicine

Urticaria, or hives, is a common mast cell–mediated condition marked by transient wheals, angioedema, or both, driven by histamine and other inflammatory mediators (1). Acute urticaria (AU) is typically self-limiting, resolving within six weeks, and is often linked to identifiable triggers such as infections, medications, foods, or physical stimuli. In contrast, chronic urticaria (CU) persists beyond six weeks and is further classified into chronic spontaneous urticaria (CSU), with no apparent trigger, and chronic inducible urticaria (CIndU), in which specific stimuli such as cold, pressure, or heat provoke symptoms (2).

Both AU and CU are associated with a spectrum of comorbidities. CSU, in particular, shows strong links to autoimmune disorders (e.g., thyroid disease, rheumatoid arthritis, systemic lupus erythematosus), atopic conditions, and psychiatric illnesses including anxiety and depression (3). Environmental and lifestyle factors such as, psychological stress, food additives, and infectionscan also precipitate flares or worsen disease activity (4,).

Recent studies have expanded understanding of urticaria subtypes, epidemiology, and pathophysiology. Wang et al. (2022) provided insight into regional variations in clinical presentation through a multicentre survey in China (5). Segú-Vergés et al. (2023) emphasized the autoimmune mechanisms of CSU (types I and IIb) and the emerging role of novel therapeutic targets, including Bruton’s tyrosine kinase and IL-4/13 inhibitors (6). Maurer et al. (2024) addressed unmet clinical needs and therapeutic development, distinguishing spontaneous from inducible forms and highlighting the substantial disease burden (7).

Despite these advances, important knowledge gaps persist. Comparative data on triggers, comorbidities, and disease patterns across AU and CU within the same study population remain limited. While regional studies exist, global comparative analyses of environmental exposures and comorbidity profiles are scarce. Moreover, most investigations focus on isolated aspects such as autoimmune mechanisms or psychosocial burden rather than providing an integrated assessment. This fragmentation limits a comprehensive understanding of how triggers interact with comorbid conditions to influence disease course across urticaria subtypes.

The present study addresses these gaps by conducting a detailed, comparative evaluation of triggering factors, associated comorbidities (including autoimmune, atopic, and psychiatric disorders), and disease patterns in both acute and chronic urticaria, encompassing spontaneous and inducible forms. By integrating clinical, environmental, and comorbidity profiles, this analysis aims to offer a holistic perspective on determinants of urticaria across diverse patient cohorts.

The present descriptive, hospital-based cross-sectional study conducted in the Department of Dermatology, Venereology and Leprosy (DVL), Mamata Academy of Medical Sciences, Hyderabad, over an 18-month period. The study was approved by the Institutional Ethics Committee and conducted in accordance with the Declaration of Helsinki.

A total of 200 consecutive patients with urticaria were enrolled, 100 with acute urticaria (AU; duration <6 weeks) and 100 with chronic urticaria (CU; duration ≥6 weeks). Chronic cases were further categorized as chronic spontaneous urticaria (CSU) or chronic inducible urticaria (CIndU).

Inclusion Criteria

• Clinical diagnosis of urticaria confirmed by a dermatologist
• Willingness to participate and provide informed consent (or guardian consent for minors)

Exclusion Criteria

• Urticarial vasculitis or other mimicking conditions
• Recent systemic immunosuppressive therapy (last 4 weeks)
• Pregnancy or lactation (if provocation tests not feasible)
• Inability to provide consent

Data Collection

Data were recorded on a structured proforma, including:

• Demographics: age, sex, occupation, residence
• History: symptom duration, frequency, nocturnal variation, recurrence, medication history, family history of atopy/autoimmunity
• Triggers: infections, drugs (NSAIDs, antibiotics), foods/additives, physical stimuli, contactants, stress, hormonal factors
• Comorbidities: atopic disorders, autoimmune diseases, metabolic syndrome components, psychiatric symptoms
• Disease Activity: Urticaria Activity Score over 7 days (UAS7) for CU patients
• Patterns: angioedema, inducible subtypes, lesion duration

Clinical Examination and Investigations

• Physical examination for active lesions, dermographism, inducible patterns
• Baseline investigations: CBC, ESR/CRP, fasting glucose, lipid profile

Statistical Analysis

Data were analyzed using SPSS v26.0.

• Continuous variables: mean ± SD or median (IQR)
• Categorical variables: frequencies and percentages
• Group comparisons: t-test/Mann–Whitney U for continuous data; Chi-square/Fisher’s exact for categorical data
• Associations: logistic regression with odds ratios and 95% confidence intervals
• p < 0.05 considered statistically significant.

Table 1: Demographic profile of study participants (n = 200)

Table 1 shows, the mean age for AU patients (34.8 ± 14.2 years) was slightly lower than CU (36.9 ± 13.7 years), consistent with trends showing chronic urticaria often peaking in the 30–50 year age range. Females predominated in both groups, more markedly in CU (65%), which aligns with autoimmune associations in CSU. Both groups showed an urban majority, reflecting hospital catchment area and possible environmental/lifestyle influences. Homemakers and skilled/office workers made up the largest proportions, followed by students and agricultural workers similar to patterns seen in previous Indian outpatient urticaria cohorts.

Table 2: Clinical history characteristics of study participants

Acute urticaria cases in this study had a much shorter symptom duration (12.4 days) compared to chronic urticaria (28.6 months). CU patients experienced more frequent attacks (>3/day in 52% vs 28% in AU), more nocturnal symptoms (56% vs 38%), and a higher recurrence rate (46% vs 14%). Recent NSAID use was common in AU, while antibiotic and ACE inhibitor exposure were less frequent. A family history of atopy (30% vs 22%) and autoimmunity (14% vs 6%) was more prevalent in CU, suggesting stronger genetic and immune-related factors in chronic disease (Table 2).

Table 3: Reported triggering factors among study participants

The table 3 compares triggering factors for acute urticaria (AU) and chronic urticaria (CU) in equal-sized patient groups. Infections were the most common trigger in AU (46%), supporting its typical short-term, infection-related nature, whereas they were less frequent in CU (9%). Drug-related triggers were more common in AU (28%) than CU (7%), while foods/additives had similar prevalence in both groups. Physical stimuli, stress, and hormonal factors were more frequently implicated in CU, reflecting its chronic, often inducible or multifactorial nature. Notably, unidentifiable triggers dominated in CU (70%) compared to AU (10%), aligning with the higher proportion of chronic spontaneous urticaria where no clear provoking factor is found.

Figure 1: Comorbid conditions among study participants

Chronic urticaria patients in this study had a higher prevalence of comorbidities than those with acute urticaria. Atopic disorders were reported in 32% of CU cases compared to 18% in AU. Autoimmune diseases, predominantly thyroid-related, were more frequent in CU (16% vs 4%), as were metabolic syndrome components (22% vs 10%). Psychiatric symptoms were also more common in CU (20% vs 8%), with anxiety (12%) and depression (8%) contributing to the burden. These patterns highlight the multifactorial nature of CU and its stronger links to systemic, metabolic, and psychological comorbidities (Figure 1).

Figure 2: Disease activity in chronic urticaria patients based on UAS7 (n = 100)

Among chronic urticaria patients, 18% had well-controlled disease (UAS7 ≤ 6), while 26% had mild activity. Moderate activity (UAS7 16–27) was the most common category, affecting 34% of patients, and 22% had severe disease (UAS7 ≥ 28). This distribution shows that over half of CU patients experienced moderate to severe activity, indicating a significant symptom burden despite treatment in some cases (Figure 2).

Table 4: Clinical patterns observed among study participants

Chronic urticaria patients more frequently presented with angioedema (42%) compared to acute urticaria cases (28%). Inducible subtypes were also markedly higher in CU (26% vs 6%), with symptomatic dermographism (10%) and cold urticaria (8%) being the most common, followed by delayed pressure and cholinergic forms. The average lesion duration was significantly longer in CU (5.2 ± 2.3 hours) than in AU (1.8 ± 0.7 hours), reflecting the more persistent nature of wheals in chronic disease (Table 4).

Figure 3: Physical examination findings among study participants

On physical examination, active wheals were observed in most patients in both groups, though slightly less in chronic urticaria (78%) compared to acute cases (84%). Angioedema was more frequent in CU (34% vs 20%), and positive dermographism was also higher (18% vs 6%), reflecting the greater presence of inducible forms. Other inducible patterns were elicited in 12% of CU patients but only 2% of AU cases. Signs of systemic disease were absent in AU and noted in 4% of CU, suggesting possible underlying autoimmune or metabolic associations in chronic disease (Figure 3).

Table 5: Baseline laboratory investigations in study participants

Baseline laboratory evaluation showed broadly similar results in both groups, though chronic urticaria patients had slightly higher inflammatory and metabolic parameters. ESR and CRP were more frequently elevated in CU (20% and 16%) compared to AU (12% and 10%), suggesting greater systemic inflammation. Eosinophilia was also more common in CU (18% vs 14%), reflecting possible atopic or allergic contributions. Metabolic indicators, including fasting glucose, total cholesterol, and triglycerides, showed higher means and a greater proportion of abnormal results in CU, aligning with its association with metabolic syndrome. Leukocytosis was marginally more common in AU (10% vs 8%), likely related to infection-driven triggers. Hemoglobin levels were comparable between groups, with mild anemia noted in a minority of patients (Table 5).

Table 6: Association between comorbidities and disease severity in chronic urticaria

* Statistically significant at p < 0.05

In chronic urticaria patients, the presence of comorbidities was significantly associated with higher disease severity. Atopic disorders were more than twice as common in the moderate/severe group (42.9%) compared to the mild/well-controlled group (18.2%). Autoimmune diseases showed the strongest link, present in 25% of patients with higher UAS7 scores versus only 4.5% in those with lower scores (p = 0.004). Metabolic syndrome and psychiatric symptoms were also significantly more prevalent in the moderate/severe category, suggesting that systemic, metabolic, and psychological factors may contribute to increased disease burden. These findings underscore the need for comprehensive comorbidity screening in CU patients, particularly those with poorly controlled symptoms (Table 6).

Table 8: Multivariable logistic regression analysis for predictors of severe CU (UAS7 ≥ 28)

* Statistically significant at p < 0.05

Multivariable logistic regression identified several independent predictors of severe chronic urticaria (UAS7 ≥ 28). Autoimmune disease presence was the strongest predictor (AOR 4.15, p = 0.023), followed by elevated CRP levels (AOR 3.82, p = 0.012). Metabolic syndrome (AOR 2.74, p = 0.046) were also significantly associated with severe disease. Atopy, elevated ESR, and psychiatric symptoms showed positive trends but did not reach statistical significance after adjustment. Age ≥ 40 years and female sex were not significant predictors. These results suggest that inflammatory and autoimmune mechanisms, along with certain metabolic and pharmacologic triggers, play a key role in determining disease severity in CU (Table 7)

In this hospital-based cohort from Hyderabad, we observed that chronic urticaria (CU) patients were slightly older than acute urticaria (AU) patients and predominantly female, a pattern repeatedly reported in epidemiologic syntheses and guidelines. CU peaking in the third to fifth decades and a female preponderance are consistent with large summaries and international guidance on urticaria epidemiology (7).

Infections were the leading reported trigger in AU (46%), whereas drug exposure particularly NSAIDs was far less common in CU (7%) compared to AU (28%). No identifiable cause was found in most CU cases (70%), consistent with the predominance of chronic spontaneous urticaria. These findings are in line with Indian hospital-based studies that similarly report AU as frequently post-infectious, while NSAID-associated flares form only a small subset of CU cases (9).

Inducible urticaria subtypes were uncommon in AU (6%) but present in one-quarter of CU (26%), with dermographism and cold urticaria most frequent aligned with the concept that chronic forms often include inducible components or comorbid inducible urticaria. Recent analyses specifically examining CSU with comorbid inducible urticaria echo our distribution of physical triggers, and guidelines emphasize careful provocation testing in suspected cases (10). Angioedema was more common in CU (42% vs 28% in AU), again paralleling descriptions in authoritative reviews (11).

In CU, most patients clustered in the mild-to-moderate range, with 22% severe (UAS7 28–42). This distribution is compatible with cohorts described in guideline-linked sources and recent therapeutic overviews, where a sizeable minority exhibit high activity despite treatment (12).

CU showed higher burdens of atopy (32%), autoimmune disease (16%; dominated by thyroid autoimmunity), metabolic syndrome components (22%), and psychiatric symptoms (20%) than AU. This pattern aligns with contemporary reviews documenting over-representation of atopic, autoimmune, and psychological comorbidity in CSU and related forms (13). Links between CU and systemic inflammation/metabolic risk are also reflected by our laboratory trends (higher ESR/CRP and lipids in CU).

AU showed slightly more leukocytosis (likely infection-related), whereas CU had higher proportions with elevated ESR/CRP and dyslipidemia. Such findings fit the differing biology of short-lived, infection-associated AU versus chronic, often autoimmune-skewed CU described in the Primer and guidelines (14).

Our AU female share and adult mean age fall within ranges reported in an acute urticaria series (mixed adult/pediatric) where middle-aged females predominated. The CU mean age, sex ratio, and the balance of spontaneous versus inducible phenotypes resemble the hospital-based multicenter survey from China, acknowledging expected regional differences in specific triggers (15). Finally, our UAS7 distribution, comorbidity burden, and angioedema frequency align with contemporary summaries and therapeutic perspectives that underscore persistent disease activity and quality-of-life impact in a subset of CU patients (16).

Strengths include parallel enrollment of AU and CU with standardized trigger and comorbidity ascertainment and bedside provocation where feasible. Notable gaps include single-center design, reliance on self-reported triggers for some categories, and absence of systematic autoantibody testing (e.g., anti-TPO for all CU) or basophil activation/autologous serum skin testing to phenotype type I vs type IIb autoimmunity (17). Future work could integrate guideline-recommended diagnostic tiers and track longitudinal outcomes (UAS7 and treatment response) to refine prognostic models.

In this 200-patient descriptive analysis, AU was most often linked to recent infections, whereas CU showed no identifiable triggers, inducible subtypes, angioedema, and greater comorbidity burden (atopic, autoimmune, metabolic, and psychiatric). CU exhibited higher inflammatory markers and a substantial moderate-to-severe UAS7 subset, consistent with contemporary literature. These findings reinforce current guidance on evaluating triggers, screening for comorbidities, and using activity scores in CU, while highlighting the need for integrated diagnostic phenotyping and longitudinal follow-up to improve individualized care.

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