||Number of patients
|Arthralgia or arthritis
|APD or PPD
|UTI or nephrolithiasis
Table I. The various factors present in the study group of chronic urticaria patients
Chronic urticaria is defined as the appearance of pruritic weals on the body, daily or on most days of a week for a period greater than six weeks. The term chronic urticaria encompasses a variety of different disorders with diverse etiologies and presentations that share wealing as the most common clinical feature. These include the physical urticaria, autoimmune urticaria and chronic idiopathic urticaria (CIU). Co-existence of physical urticaria with CIU or autoimmune urticaria occurs frequently. Angioedema occurs concurrently with chronic urticaria in 87% patients with CIU and is also frequent in autoimmune urticaria. An overall average lifelong prevalence of chronic urticaria is estimated to be about 1-2%. Urticaria can be highly distressing and can cause personal, social and occupational disability [1-4]. Most patients with chronic urticaria have been found to have an endogenous rather than an exogenous cause of illness. There is a wide range of secondary external aggravating factors that can bring out weals and angioedema in patients with chronic urticaria especially pressure; friction; drugs eg NSAIDS; foods and food additives like tartrazine and other azo dyes; infections/infestations like intercurrent viral infections, intestinal parasites; inhalants like grass pollen, animal danders, house dust; implants like metal pin, metal dental prosthesis and systemic diseases especially connective tissue diseases [5-8]. A good number of cases may be idiopathic with auto immunity being recognized as an increasingly important cause. Sera of approximately 60% of patients with chronic urticaria cause a pink weal, probably due to histamine release, when injected intradermally into the patient’s own skin (the autologous serum skin test). Infact sera of about 30-50% patients with chronic urticaria released histamine in vitro from basophils and skin slices obtained from healthy people implying presence of circulating serum histamine releasing factor. This activity has been found to be due to functional IgG antibodies directed against α-subunit of high affinity IgE receptors (FcεRI-α) or less frequently against receptor bound IgE. In some patients the histamine-releasing factor is mast cell specific and is a non-immunoglobin which is not inhibited by preincubation with FcεRI or IgE [9-13]. It has also been found that normal subjects with history of acute urticaria induced by several NSAIDs show a positive reaction to intradermal injection of autologous serum, a phenomenon observed in patients with CIU and suggests a possible common background in CIU and NSAID induced urticaria. A relation between these two conditions is further suggested by the fact that up to 30% of the patients with chronic urticaria have worsening of their skin disorder after ingestion of chemically unrelated NSAIDs. A study conducted in these normal subjects with NSAID intolerance revealed a propensity to develop chronic urticaria in 33% over a follow up period of 1-10 years . The treatment of chronic urticaria can be quite challenging. Anti-histamines are the first-line treatment for all patients with chronic urticaria. Three main groups of anti-histamines used singly or in combination include the classical sedating H1, non-sedating second generation H1 and their derivatives and the H2 antihistamines. Second generation anti-histamines are preferred to first generation H1 anti-histamines in the treatment of chronic urticaria because of their lack of sedation, impairment of cognitive and psychomotor performance and other side effects. In a fraction of cases treatment is inadequate. In these patients with unremitting disease, non- conventional modalities are tried. These include dapsone, doxepin, epinephrine, prednisolone, sulfasalazine, thyroxine, montelukast, cyclosporine, intravenous immunoglobulins, plasmapheresis and immunosuppressants [15,16]. As urticaria symptoms can have a profound effect on a patient’s quality of life (QoL); therefore, treatment should address both relief of physical symptoms and improvements in QoL. Erbagci Z.  conducted a randomized single-blind placebo-controlled study in 30 patients of chronic refractory urticaria. The medication was given in a cross-over manner over 12 weeks as adjunctive treatment to an anti-histamine (H1). After informed consent, 2 groups were made. Group A received montelukast 10 mg once a day for six weeks followed by crossover to 6 weeks on placebo and a non-sedating antihistamine as needed. In Group B administration was reversed. Urticaria activity score (UAS) and visual analogue score (VAS) was used to monitor the response. No side effects were noted. H1 antihistamine intake was significantly less frequent during montelukast period (p<0.01). Statistically significant difference in UAS and VAS (p<0.01, p<0.05) between montelukast and placebo periods was seen. Thus montelukast was found to be a safe and effective adjuvant to anti-histamines in urticaria. In our patients montelukast was effective in majority of cases and the adjunctive intake of levocetirizine was reduced. Moreover the drug was well-tolerated with minimal side-effects. It was found especially useful in the patients on NSAIDS. Urticaria has been known to be caused by a number of pathophysiological mechanisms. These include immunological IgE and IgE-receptor dependent urticaria; urticaria mediated by complement and other effector systems; urticaria after direct mast cell degranulation; urticaria relating to abnormalities of arachidonic acid metabolism and idiopathic urticaria. Leukotrienes play a pivotal role in NSAID induced urticaria. Leukotriene receptor antagonists block the action of these and hence their benefit in aspirin sensitive urticaria. In our study twenty-two patients had a good response, four showed moderate and five patients had no response. A quick relapse was seen in atopics and ASST positive patients indicating perhaps the need for a longer therapy. In conclusion montelukast seems a promising option both in terms of safety and efficacy in chronic urticaria. It is well worth a trial in these patients.
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