Correlation between the histopathology of chronic urticaria and its clinical picture*

BACKGROUND Chronic urticaria is characterized by transient, pruritic lesions of varying sizes, with central pallor and well-defined edges, with disease duration longer than six weeks. Its cellular infiltrate consists of neutrophils, lymphocytes and eosinophils. There is a subgroup of patients with eosinophilic or neutrophilic urticaria, resistant to the treatment with antihistamines, but that respond to a combination of antihistamine with other drugs. OBJECTIVE To evaluate the present infiltration in chronic urticaria biopsies and correlate it with the clinical disease activity and response to treatment. METHODS Forty-one patients with chronic urticaria were classified according to the score of severity of the disease, response to treatment and type of perivascular infiltrate. Inflammatory infiltrates were divided in eosinophilic (46.30%), neutrophilic and mixed. RESULTS An association was found between the eosinophilic infiltrate and clinical scores of greater severity (p = 0.002). CONCLUSION This association shows that the eosinophilic inflammatory infiltrates denote high clinical activity, which means more severe and exuberant clinical pictures of the disease.


INTRODUCTION
Urticaria is one of the most commonly conditions observed in dermatology daily practice, affecting 15% to 30% of the population. 1 Wheal is its elementary dermatological lesion, characterized by being itchy and have central edema with varied size, surrounded by a reflex erythema and with ephemeral nature; furthermore, the skin returns to its normal aspect usually in a period that varies from one to 24 hours. 2 Urticaria is classified, from the point of view of duration of its evolution, in acute (less than six weeks) or chronic (over six weeks). 3 The physiopathology of chronic urticaria (CU) has long been associated with anxiety and allergy to foods or its additives, but today it is considered the participation of autoimmune mechanisms and coagulation factors. 4 It is known that degranulation of mast cells or skin basophils is its initial stimulation. By releasing potent vasoactive mediators, vasodilation is induced, increasing capillary permeability and resulting in erythema and papule formation. 5 The The clinical importance of characterizing the inflammatory infiltrate resides in the presence of a subgroup of patients presenting eosinophil or neutrophil urticaria, which may be resistant to treatment with antihistamines, but which responds to a combination of antihistamine with other drugs. 6 In addition to the improvement and optimization of the treatment of disease, to establish a relation between inflammatory infiltrate and clinical score of severity of the disease can also aid in the prognosis of the disease and therefore in its management. The aim of this study is to evaluate the inflammatory infiltrate present in CU biopsies and correlate it with the clinical activity of the disease and its response to treatment.

This is a cross-sectional, descriptive study of clinical basis.
We To meet the inclusion criteria, patients had to: 1) come from the urticaria clinic; 2) present or have presented the disease for a period longer than six weeks; 3) be older than 18 years; 4) understand and sign the informed consent form; and 5) have undergone biopsy at some time of the disease.

DISCUSSION
Our study showed a higher percentage of female patients, which is in accordance with the demographic profile of the disease that is already known, but the proportion found was 5.84 women for one man, while in literature the proportion is 2:1. 9 The type and  infiltrate types manifested clinically in a mildest form. 11 The tissue factor expressed by eosinophils induces the activation of blood clotting and thrombin generation, which, in turn, can increase vascular permeability, both directly, acting on endothelial cells, and indirectly, inducing mast cell degranulation by the release of histamine. 12 Thus, the association found in this study between the clinical score of greater severity and eosinophil infiltrate shows that, when the eosinophil predominates, there is more than an activation pathway of the disease -the direct and also the indirect -reinforcing its development and aggravating its clinical picture.
In our study, the relation between the type of infiltrate and response to treatment wasn't identified. Urticaria presents a wide range of etiologies, and its onset comes from different cellular activation orders. Thus, the therapeutic response is very variable and susceptible to idiosyncrasies, because each patient has a trigger mechanism of the disease.
In our study, no statistical significance between the values of IgE and the types of inflammatory infiltrate was found, but the median IgE in eosinophilic infiltrate presented higher than in the other infiltrates. IgE is produced by plasma cells, has a short mean life and receptors in various inflammatory cells, among them mast cells and basophils, which have specific Fc receptors. 11 Mast cells are potent inflammatory cells that express on their surface receptors able to start, expand and perpetuate inflammatory processes by releasing soluble factors and that interact with other immune effector cells. 11 In our study, no relation between D-dimer and inflammatory infiltrate was evidenced, although there is in the literature a relation between disease severity and high plasma levels of D-dimer. 4 Also, relation between values of CRP and infiltrate was not identified, but this is a unspecific marker of systemic inflammation. 13

CONCLUSION
In our study, we found significant statistical relation be- Relation between the findings of biopsies and response to treatment of urticaria was not demonstrated. Also, the study didn't find significant statistical relation between the infiltrate and CRP, D-dimer and IgE variables.q