www.landesbioscience.com Dermato-Endocrinology 255
Dermato-Endocrinology 3:4, 255-258; October/November/ 2011; © 2011 Landes Bioscience
Idiopathic chronic urticaria
and thyroid autoimmunity
Experience of a single center
*Correspondence to: Vincenzo Nuzzo; email@example.com
Submitted: 10/01/11; Accepted: 10/29/11
Urticaria is defined as a widespread, fugacious, itchy cutaneous
swelling; it is one of the most frequent dermatosis, being its prev-
alence in general population estimated about 20%.1 Urticaria is
regarded as idiopathic in approximately 75% of affected patients.1
Chronic form is defined as at least 6-week history of the disorder
and chronic urticaria (CU) was observed in about 25% of the
An increase prevalence of autoimmune diseases was observed
in subjects with CU.2-8 Thyroid autoimmune thyroiditis and
Hashimoto’s thyroiditis were described among patients with
CU, and increased serum levels of antithyroid antibodies were
reported with frequency ranging between 12–29% in different
Although number of authors reported on the association
between CU and thyroid autoimmunity, there are not yet avail-
able data regarding this association in areas with mild-to-moder-
ate iodine deficiency.2-9 The present study attempts to address this
issue. This prospective case-control study is aimed at determin-
ing the prevalence of thyroid autoimmune disorders in a cohort
of patients with CU, all living within the province of Naples,
Urticaria is one of the most frequent dermatosis, being its prevalence in general population estimated about 20%. This
prospective case-control study was aimed at determining the prevalence of thyroid autoimmune disorders in a cohort of
patients with chronic urticaria (cU), all living within an area with mild-to-moderate iodine deficiency. Fifty four consecutive
patients affected by cU were recruited and compared to 108 healthy controls. assessment of the thyroid function
included measurement of serum concentrations of Tsh, FT3, FT4, anti-thyreoglobulin (anti-TG) and anti-peroxidase (anti-
TpO) antibodies. Ultrasound scan of the thyroid gland was performed in all subjects using a 7.5 Mhz linear transducer. all
subjects were followed up for 6 months. 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. however, presence of antibodies
or thyroiditis does not seem to influence clinical course of cU. These results suggest that screening for thyroid function
may be useful in all the patients with cU.
Vincenzo Nuzzo,1 Libuse Tauchmanova,2 paola colasanti,3 alfonso Zuccoli¹ and annamaria colao²
1Internal Medicine Unit; 2Dermatology Unit; “s. Gennaro” hospital; Naples, Italy; 3Department of Molecular and clinical Endocrinology and Oncology;
“Federico II” University of Naples; Naples, Italy
Keywords: urticaria, Hashimoto’s thyroiditis, iodine deficiency
Thyroid autoantibodies were detected in 12 of the 54 patients,
all females (Table 1); their mean age was 31.5 years (median: 27
yrs, range: 21–47 years). As shown in Table 1, 6 out of these 12
patients had increased levels of anti-TPO antibodies and 6 others
had increased both anti-TPO and anti-TG antibodies.
Ten of the 12 patients (18.5%) with positive thyroid autoan-
tibodies were also found as being affected by hypothyroidism.
Diagnosis of chronic thyroiditis was confirmed by thyroid ultra-
sound by a picture of non-homogeneous hypoechoic pattern with-
out nodules.11 Two of affected patients were sisters. Hypothyroid
patients were given replacement therapy with L-thyroxine (100
+/- 12.50 mcg daily).
We did not observed any difference in the clinical features
of CU between patients with and without thyroid autoantibod-
ies, when considering the frequency of the crises, association of
urticaria with angioedema and resistance to antihistaminic treat-
ments (Table 2).
Only 7 controls had detectable anti-thyroid antibodies (Table
3); 2 had increased anti-TPO antibodies, other 2 had anti-TG
antibodies and 3 other subjects had both anti-TPO and anti-TG
antibodies. One of them was hypothyroid.
256 Dermato-Endocrinology Volume 3 Issue 3
Comparing patients to controls, thyroid autoantibodies
were more frequently found in patients (22.2%, p = 0.0074).
Moreover, patients with CU developed hypothyroidism more
frequently than controls (18.5%, p = 0.0001).
Significantly increased ANA levels were observed in 4 out of
10 patients affected by Hashimoto’s thyroiditis (Table 1). One
of them developed lupus erythematous discoid (LED) during
the 6-month period of observation. No other abnormality in the
biochemical tests was revealed among our patients with autoim-
mune thyroid disorders.
In 10 patients without thyroid autoimmunity, an increase
in total IgE and/or specific IgE was revealed. In particular, 6
patients had an increase in total IgE; one patient had IgE anti-
bodies directed against some inhalant and/or food allergens and
3 patients had an increase in both total IgE and some specific IgE
Iodine urinary excretion was similar in patients and healthy
controls; they were both in the lower third of the normal range.
Median urinary iodine excretion was below 55 mcg/l that was
found by Aghini-Lombardi et al. in an iodine-deficient area of
Discussion and Conclusions
In this prospective, case-control study we evaluated the associa-
tion 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
Table 1. Thyroid antibodies and thyroid function, c3, c4, immunoglobulin, Rheumatest, aNa, ENa in patients with chronic urticaria
PatientsSexAge FT3FT4 TSH Ab-TG Ab-TPO C3 C4RF ANAENA Diagnosis
2F 242.6511.80.4 463 >8000NNN negneg
3F 303.139.5 7.54 neg345NNN negneg
5F 47 2.01 13.15.41neg465NNN negneg
8F 45 6.112.5 1.46375461NNN 1/160 Neg
17F21 5.6510.8 5.21 494392NNN 1/160
Isolated positivity of
32F 22 4.15 11.06.01421420NNN1/160neg
36F442.1112.35.75441 542NNN1/160 neg
42F 234.9412.8 2.34neg 357NNN Negneg
Isolated positivity of
49F29 2.1611.2 7.63 neg 327NNN negneg
52F 252.58 10.25.38 585894NNN Neg Neg
54F 461.97 9.2 5.38 neg489NNNNegNeg
www.landesbioscience.com Dermato-Endocrinology 257
thyroid autoimmunity also in the area of iodine
deficiency.2-5, 7-8 However, presence of antibod-
ies 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 thy-
roiditis 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 thy-
roiditis 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 auto-
antibodies 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
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 iodin-
ation may account for different immunological properties with
the generation of new epitopes that provide greater immunoge-
nicity 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 evalu-
ating 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 symp-
toms 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 treat-
ment with L-thyroxine had no influence on the clinical course of
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 affin-
ity 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 autoim-
mune 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 patho-
genesis 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 auto-
antibodies and Hashimoto’s thyroiditis in patients with CU were
22% and 18.5%, respectively. These results suggest that screen-
ing 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.
Patients and Methods
Patients. This is a prospective case-control study that enrolled
patients and controls during 6 months, from December to July
2007, and followed all of them for further 6 months.
Table 2. clinical features of the urticaria in patients according to the presence
of anti-thyroid autoantibodies
N. patients with crises less
than once a day more than 3
times a week
N. patients with less than
crises 3 times a week
28 8 0.99
14 4 0.99
Association with angio-
18 4 0.74
Resistance to antihistamines
34 7 0.13
Table 3. clinical features of the urticaria in patients according to the presence
of anti-thyroid autoantibodies
Patients with chronic
Positivity of thyroid
N. patients with less than
crises 3 times a week
12 (22.2 %)7 (6.5 %)0.99
10 (18.5 %)2 (1.8 %) 0.0005
10 (18.5%)1 (0.9%) 0.0001
8 (15%)0 (0%)0.0002
2 (3.7%) 1 (0.9%)0.53
258 Dermato-Endocrinology Volume 3 Issue 3
Ultrasound scan of the thyroid gland was performed in all
subjects using a 7.5 MHz linear transducer.
The patients were followed up for 6 months after the study
entry to observe the course of urticaria and eventual appearance of
other autoimmune diseases.
All controls underwent the same evaluation at the study entry;
their medical history, physical examination and biochemical
tests excluded any previous or current urticaria. They were also
followed for 6 months after their initial evaluation, in order to
exclude any new onset of urticaria or other disorder.
Assays. Determinations of thyroid hormones, TSH and anti-
bodies were performed with the same commercial kits for the
whole study period. Serum TSH was measured using an immuno-
radiometric assay (Delfia, Wallac, Inc. Finland) and free thyroid
hormones were determined by radioimmunoassay Lisophase kits
(Technogenetics, Milan, Italia). Anti-TG antibodies were mea-
sured with an Ares Serono kit (Milan, Italy) and anti-TPO anti-
bodies by a DiaSorin kit (Saluggia, Italy). Iodine urinary excretion
was measured in extemporaneous morning samples using the col-
orimetric ceric ion arsenious acid wet ash method based on the
Sandell-Kolthoff reaction (10) and spectrophotometer equipped
with an automatic sipper. The intra-assay variation coefficient was
<3.6% and the inter-assay one <7.8% for all the measurements.
Blood chemistry profile, blood count, and liver and kidney
function were analyzed using a standard autoanalyzer.
Statistical analysis. All statistical procedures were performed
using a Statistical Package for Windows (Sigma-Stat). The dif-
ferences between patients and controls were compared by using
the Pearson’s chi-square test for categorical variables. All results
are given as percentage, media, median, standard deviation and
range. Statistical significance was set at 5%.
Disclosure of Potential Conflicts of Interest
No potential conflicts of interest were disclosed.
Fifty-four consecutive patients affected by CU were recruited
at the outpatient clinic of Allergological Dermatology; there
were 42 females and 12 males, with a median age of 36 years
(range, 15–58 years), all were living in the province of Naples.
For each patient enrolled, two control subjects matched for
age and gender were selected among the population of usual
blood donors and included in the data analysis. Indeed, the
control group consisted of 108 healthy individuals (84 females
and 24 males, median age 35 years (range, 18-59 years); with-
out history of urticaria. All control subjects lived within the
same geographic area.
None of the 162 subjects were taking any drugs or had his-
tory of other autoimmune diseases.
The study was performed according to the procedures indi-
cated by the Helsinki II Declaration. All enrolled subjects gave
their informed consent to participate in the study.
Methods. All the patients underwent a complete medical
and pharmacological anamnesis, a complete physical examina-
tion, a dermatological objective examination to reveal eventual
presence of other skin disorders.
Biochemical evaluation included a routine laboratory
screening with complete blood count, erythrocyte sedimenta-
tion rate (ESR), C-reactive protein (CRP), Antistreptolysin O
titre, glucose levels, liver and kidney function tests, electro-
phoresis of serum proteins), Rheumatoid factor (RF), C3 and
C4 components of the complement system, immunoglobulin,
cryoglobulin, HBsAg, HCV-Ab, VDRL, antinuclear antibodies
(ANA), anti-extractable nuclear antigens (ENA), total IgE, IgE
antibodies directed towards mixed food and inhalant allergens
and parasitological evaluation of the stool (on 3 samples col-
lected in 3 days). Assessment of the thyroid function included
measurement of serum concentrations of TSH, FT3, FT4,
anti-thyreoglobulin (anti-TG) and anti-peroxidase (anti-TPO)
1. Kozel MM, Sabroe RA. Chronic urticaria: aetiology,
management and current and future treatment options.
Drugs 2004; 64:2515-36.
Palma-Carlos AG, Palma-Carlos ML. Chronic urticaria
and thyroid auto-immunity. Allerg Immunol 2005;
Verneuil L, Leconte C, Ballet JJ, Coffin C, Laroche D,
Izard JP, et al. Association between chronic urticaria
and thyroid autoimmunity: a prospective study involv-
ing 99 patients. Dermatology 2004; 208:98-103.
Levy Y, Segal N, Weintrob N, Danon YL. Chronic
urticaria: association with thyroid autoimmunity. Arch
Dis Child 2003; 88:517-9.
Turktas I, Gokcora N, Demirsoy S, Cakir N, Onal E.
The association of chronic urticaria and angioedema
with autoimmune thyroiditis. Int J Dermatol 1997;
Collet E, Petit JM, Lacroix M, Bensa AF, Morvan C,
Lambert D. Chronic urticaria and autoimmune thyroid
diseases. Ann Dermatol Venereol 1995;122:413-6.
Leznoff A, Sussman GL. Syndrome of idiopathic
chronic urticaria and angioedema with thyroid autoim-
munity: a study of 90 patients. J Allergy Clin Immunol
8. Leznoff A, Josse RG, Denburg J, Dolovich J. associa-
tion of chronic urticaria and angioedema with thyroid
autoimmunity. Arch Dermatol 1983; 119: 636-40.
Aversano M, Caiazzo P, Iorio G, Ponticiello L, Lagana
B, Leccese F. Improvement of chronic idiopathic urti-
caria with L-thyroxine: a new TSH role in immune
response? Allergy 2005; 60:489-93.
10. Sandell EB, Kolthoff IM. Micro determination of
iodine by a catalytic method. Mikrochemica Acta 1937;
11. Rago T, Chiovato L, Grasso L, Pinchera A, Vitti P.
Thyroid ultrasonography as a tool for detecting thyroid
autoimmune diseases and predicting thyroid dysfunc-
tion in apparently healthy subjects. J Endocrinol Invest
12. Aghini-Lombardi F, Antonangeli L, Martino E, Vitti
P, Maccherini D, Leoli, et al. The spectrum of thy-
roid disorders in an iodine-deficient community: the
Pescopagano survey. J Clin Endocrinol Metab 1999;
13. Vitti P, Delange F, Pinchera A, Zimmermann M, Dunn
JT. Europe is iodine deficient. Lancet 2003; 361:1226.
14. Fenzi GF, Giani C, Ceccarelli P, Bartalena L, Macchia
E, Aghini-Lombardi F, et al. Role of autoimmune and
familial factors in goiter prevalence. Studies performed
in a moderately endemic area. J Endocrinol Invest
15. Saboori AM, Rose NR, Bresler HS, Vladut-Talor M,
Burek CL. Iodination of human thyroglobulin (Tg)
alters its immunoreactivity. Iodination alters mul-
tiple epitopes of human Tg. Clin Exp Immunol 1998;
16. Dreskin SC, Andrews KY. The thyroid and urticaria.
Clin Immunol 2005; 5:408-12.
17. Vermeulen C, Mathelier-Fusade P, Rouquette AM,
Bayrou O, Pecquet C, Leynadier F. Chronic urticaria,
thyroiditis and autologous serum test. Ann Dermatol
Venereol 2003; 130:1115-8.
18. Rottem M. Chronic urticaria and autoimmune thyroid
disease: is there a link? Autoimmun Rev 2003; 2:69-72.
19. O’Donnell BF, Francis DM, Swana GT, Seed PT,
Kobza Blak A, Greaves MW. Thyroid autoimmunity in
chronic uticaria. Brit J Dermat 2005; 153:331-5.
20. Levy Y, Segal N, Weintrob N, Danon YL. Chronic
urticaria: association with thyroid autoimmunity. Arch
Dis Child 2003; 88: 517-9.