In this prospective, case-control study we evaluated the association between CU and thyroid autoimmunity in an area with mild-to-moderate iodine deficiency. The prevalence of thyroid antibodies was significantly higher in our cohort of patients with CU than in controls (22% vs. 6.5 %). Hashimoto's thyroiditis was also more frequent in patients than controls (18.5% vs. 1.8%). These frequencies do not differ from those previously reported by some other authors and confirm the association between CU and thyroid autoimmunity also in the area of iodine deficiency.2–5, 7–8
However, presence of antibodies or thyroiditis does not seem to influence clinical course of CU, as suggested by similar frequencies and features of the crises among patients with or without thyroid autoimmune disorders.
According to other reports, both CU and thyroiditis occurred more frequently in women than men; therefore, also the association of these two disorders was more frequent in women. However, we can not exclude a gender-related bias.3,7
Thyroid autoimmune disorders in patients with CU may appear with variable features, ranging from a simple positivity of thyroid autoantibodies to a lymphocytic thyroiditis or Hashimoto's thyroiditis with or without hypothyroidism.2–9
Such an association was first described by Leznoff et al. in 1983 who observed that 12% of patients with CU were also affected by autoimmune thyroiditis.8
Since then, the prevalence of positive thyroid autoantibodies ranged from 12 to 29% in patients with CU in different studies.2–5, 7–8
Interestingly, no case of Graves disease was described among patients with urticaria.
The role of geographical area has never been investigated regarding this issue, in particular, there are no literature data regarding the frequency of the association in areas of mild-to-moderate iodine deficiency, such as Southern Italy.13
In these areas, a higher prevalence of antithyroid antibodies occurs in general population.14
This may be related to a prolonged TSH-stimulated release of thyreoglobulin with increased immunogenicity in the bloodstream. Indeed, a variable degree of thyreoglobulin iodination may account for different immunological properties with the generation of new epitopes that provide greater immunogenicity to the molecule.15
The only data regarding the association of thyroid autoimmunity and CU in the province of Naples were provided by Aversano et al.9
However, these authors evaluated the effects of L-thyroxine on the CU outcome in patients affected by autoimmune thyroiditis, and their study was not aimed at evaluating the prevalence of thyroid disorders among patients with CU.
The effects of replacement treatment for hypothyroidism on clinical symptoms of urticaria are still controversial. Leznoff et al. reported that the L-thyroxin therapy improved clinical symptoms of CU.7
Some studies confirmed this observation, while other authors failed to find any influence of L-thyroxine on the course of urticaria.9,16,17
In our patients with thyroiditis, the treatment with L-thyroxine had no influence on the clinical course of urticaria.
Mechanisms that link thyroid autoimmunity and CU are still unknown and are object of controversies.18
It was shown that thyroid autoantibodies do not induce urticaria and are only an epiphenomenon. CU may have autoimmune basis, since as many as 5–69% of the patients have autoantibodies to the high affinity receptor for IgE (anti FcεRI) on mast cells and basophils, these antibodies may be pathogenetic in the onset of CU.18–20
No other etiology of CU except for the autoimmune one was revealed among our patients.
Other biochemical tests that were carried out in our patients were aimed at evaluating of association with other autoimmune disorders, in particular, diseases of the connective tissue. Positivity of ANA (>1:160) that was found in 4/10 patients with Hashimoto's thyroiditis and development of lupus erythematous discoid in one of them further confirms the autoimmune pathogenesis of CU.
In conclusion, results from the present study confirms the high prevalence of thyroid autoimmune disorders in patients with CU and extends the finding on the population with mild-to-moderate iodine deficiency. Indeed, in the province of Naples, an area with iodine deficiency, the prevalence of antithyroid autoantibodies and Hashimoto's thyroiditis in patients with CU were 22% and 18.5%, respectively. These results suggest that screening for thyroid function may be useful in all the patients with CU. Non symptomatic positivity of antithyroid antibodies is a serological markers for chronic thyroiditis that represents a risk factor for development of hypothyroidism. Predictive value of this association remains to be elucidated.