Multiple comorbidities in patients with long-lasting chronic spontaneous urticaria

hronic Spontaneous Urticaria (CSU) is a mast cell-driven kin disease, and mast cell degranulation is triggered by the ctivation of several receptors on its surface. IgE-Fc RI comlex appears to be involved in the autoimmune etiology of SU, through the presence of IgG anti-Fc RI, anti-IgE or IgE gainst autoallergens, but many other receptors can induce ast cell degranulation, as such as Mas-Related G-Proteinoupled Receptor X2 (MRGPRX2).1--3 Several types of comorbidities are associated with CSU these patients had more often multimorbidities, including the components of MetS (p < 0.05). Eight comorbidities were assessed in this study, the frequency of them in the same patient ranged from 0 to 6 comorbidities (Fig. 1). The most frequent comorbidities were respiratory disorder (rhinitis and/or asthma) in 82 (47.4%), followed by high blood pressure, in 54 (31.2%), and dyslipidemia, in 38 (22%) patients. There was a correlation between the duration of CSU and the frequency of comorbidities, r2 = 0.043, p = 0.007 (Fig. 2). Patients with CSU refractory to antihistamine had a higher frequency of angioedema, gastrointestinal disorders, and obesity, compared to those patients responsive to antihistamine (77.8% versus 60.2%, p = 0.045; 28.9% versus 13.3%, p = 0.017; and 26.7% versus 16.4%, p = 0.039, respectively). In the present study, 16 (9.2%) patients had CSUassociated autoimmune diseases, a frequency higher than that observed in the general population (around 5%).6 Of the 16 patients, autoimmune thyroid disease represented 87.5% of them. However, we did not find an increase in its frequency as CSU lasted longer or with disease severity. One explanation would be that the mean age in the studied groups, according to the duration of CSU, was similar (mean of 49.8 years), reinforcing that the frequency of autoimmune diseases increases with age.4 Multimorbidity is associated with a poor quality of life; patients are at higher risk of severe clinical outcomes. CSU is nowadays considered a low-grade inflammatory systemic disease. The proposed pathomechanism would be the constant or continuous activation of mast cells observed in p m p t p p p p b 1

these patients had more often multimorbidities, including the components of MetS (p < 0.05).
Eight comorbidities were assessed in this study, the frequency of them in the same patient ranged from 0 to 6 comorbidities ( Fig. 1). The most frequent comorbidities were respiratory disorder (rhinitis and/or asthma) in 82 (47.4%), followed by high blood pressure, in 54 (31.2%), and dyslipidemia, in 38 (22%) patients. There was a correlation between the duration of CSU and the frequency of comorbidities, r 2 = 0.043, p = 0.007 (Fig. 2).
In the present study, 16 (9.2%) patients had CSUassociated autoimmune diseases, a frequency higher than that observed in the general population (around 5%). 6 Of the 16 patients, autoimmune thyroid disease represented 87.5% of them. However, we did not find an increase in its frequency as CSU lasted longer or with disease severity. One explanation would be that the mean age in the studied groups, according to the duration of CSU, was similar (mean of 49.8 years), reinforcing that the frequency of autoimmune diseases increases with age. 4 Multimorbidity is associated with a poor quality of life; patients are at higher risk of severe clinical outcomes. CSU is nowadays considered a low-grade inflammatory systemic disease. The proposed pathomechanism would be the constant or continuous activation of mast cells observed in patients with uncontrolled CSU. In addition to the autoimmune mechanism described for mast cell activation in patients with CSU, several other factors maintain or worsen the mast cell activation. 9,10 In the present study, three components or more of MetS were observed more frequently in patients with six years or more of CSU, compared with those patients with one to five years of disease (15.9% versus 1.3%, p < 0.001). The most common component of MetS was high blood pressure (31.2% of 173 patients), and around 10% of 173 patients had at least three of them.
In conclusion, this study showed that patients with earlyonset and long-lasting CSU had more often comorbidities including three or more components of MetS. The present study has shown that almost half of the participants had at least one component of MetS. Three or more components of MetS had a statistically significant higher frequency in patients with CSU lasting six or more years. Long-lasting CSU, and probably, uncontrolled disease, could evolve with multimorbidities, suggesting that early complete control of CSU would be essential to prevent this outcome. These results need further prospective research to highlight the importance of CSU as a low-grade inflammatory disease. The present results suggest an association between long-lasting CSU and MetS, but case-control trial studies should be essential to confirm the our conclusions, further including a larger number of participants.

Financial support
None declared. Anti-Inflammatory Drugs, NS, Non-significant The Kruskal-Wallis test for current age and age at onset of CSU. 2 analysis for gender, CIndU, angioedema, NSAID exacerbated CU, and refractoriness to antihistamine.

Conflicts of interest
None declared.

Acknowledgment
We He denied any symptoms, or history of trauma, and had not noticed this deformity (Fig. 1).
The second case was a 54-year-old woman with a diagnosis of rosacea, who consulted due to a recent flare. As a coincidental finding, PBN deformity of the fifth left fingernail was recognized. She had a history of left-hand trauma with a knife when she was eight years old (Fig. 2). He stated these changes were caused by the explosion of homemade fireworks at the age of thirteen (Fig. 3).
Kandil was the first one that described this deformity back in 1971, naming it due to its resemblance to a parrot beak. He reported an idiopathic over the curvature of two fingernails in a 38-year-old woman.