INTRODUCTION

Chronic urticaria (CU) is a pruritic skin condition characterized by wheals and/or angioedema lasting for at least six weeks or longer [1]. It is a common cause in patients presenting to primary care, emergency rooms, and dermatologists [2]. With a point prevalence of 0.5-1% in the population, it is one of the most common skin disorders encountered [3].

Chronic urticaria may severely affect the quality of life of the patient, due to the duration of symptoms, which may persist for years [4]. Nearly half of the patients have persistent symptoms even after three years of onset [5].

The release of histamine and other inflammatory mediators from mast cells causes an acute inflammatory response, including vasodilatation, increased fluid permeability, and the recruitment of various cells, which constitute the basic pathogenesis of the disease [1].

In CU, autoimmunity plays a major role. In a subset of patients, the coagulation cascade is also activated through the extrinsic pathway, which may increase plasma D-dimer levels [6,7].

Recent studies have demonstrated the correlation between plasma D-dimer levels and CU, suggesting the possibility of the use of plasma D-dimer levels as a biomarker for disease activity and response to treatment in patients with CU [8–11].

There is a paucity of data concerning plasma D-dimer levels in Kashmiri patients with CU. This study investigates the relationship between plasma D-dimer levels and disease activity in a Kashmiri population.

MATERIALS AND METHODS

This study was conducted after receiving clearance from the institutional ethical committee. A total of 120 patients with CU (more than two episodes a week for more than six weeks) who visited the outpatient department of dermatology of the Government Medical College in Srinagar, India, from November 2020 to July 2021, aged at least eighteen years, and clinically diagnosed with CU were included in the study. Patients with diseases or taking medications that could have altered the coagulation pathways were excluded from the study.

A total of fifty age- and sex-matched healthy subjects undergoing routine check-ups comprised the control group.

All cases and controls voluntarily agreed to participate in the study and signed a written consent form. Demographic data and personal, family, and medical histories were recorded.

RESULTS

Correlation between Plasma D-Dimer Levels and Disease Severity

The patients were divided into three groups: < 1 year, 1-5 years, and > 5 years. It was noted that D-dimer levels in patients who had a longer duration of the disease were significantly higher (p < 0.05).

The difference in the proportion of abnormal plasma D-dimer levels in the patients with CU and the control group was statistically significant (60.8% vs. 44%; p = 0.04) (chi-squared test: 4.05). Plasma D-dimer levels were significantly higher in the patients with CU than in the control group (720.5 ng/mL vs. 405.6 ng/mL; p < 0.001). Table 1 shows disease severity and plasma D-dimer levels among all groups.

Table 1: Disease severity and plasma D-dimer levels among all groups.

DISCUSSION

It is imperative to find reliable biomarkers to assess disease severity when determining the correlation between disease severity and treatment response. A study by Raffael et al. [11] found that disease severity may also predict the duration of chronic spontaneous urticaria.

Studies have shown a link in the pathogenesis of CU with the activation of the coagulation cascade [7,12,13]. The activation of this cascade results in thrombin formation and the activation of mast cells. This leads to the release of histamine from mast cells and causes edema formation in urticaria [7]. D-dimer, which is an FDP (fibrin degradation product) is formed after the lysis of thrombus. It may remain elevated in the serum for around one week [14].

In our study, we observed higher D-dimer levels in the patients with CU than in the control group. Similar results were found in other studies conducted in other regions [8,10,14]. Thus, our study provides further evidence of a possible mechanism of coagulation cascade activation in patients with CU.

Our study demonstrated statistically higher plasma D-dimer levels and a higher proportion of abnormal plasma D-dimer levels in patients with CU. This was corroborated in a study by Asero et al. [15]. This finding is also supported by a literature review by Pavel et al. [16].

D-dimer levels and CRP show a strong correlation with CSU activity [16]. Our study also found a positive correlation between disease severity and serum D-dimer levels. Hence, D-dimer may play a vital role as a biomarker for CU severity. Besides, D-dimer levels in the plasma may also be employed to assess treatment response and potential antihistamine resistance to CU [17]. Therefore, D-dimer may be a predictor of response to treatment, more so in refractory cases or antihistamine-resistant CU.

Although several studies show a possible correlation between plasma D-dimer levels and CU, larger studies are needed due to the lack of strong evidence.

CONCLUSION

In our study, the patients with CU had higher plasma D-dimer levels than the control subjects, and the levels of D-dimer were higher in more severe cases. D-dimer levels may be considered a biomarker for disease activity/severity.

REFERENCES

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