Discussion
The lifetime prevalence of acute urticaria is estimated to be 15-23% in
adults and up to 14.5% in children5. The detriment to
quality of life is severe, and applicable to social, recreational,
vocational and emotional aspects of life6,7.
Management consists of high dose anti-histamines along with steroid use
and avoidance of causative factors8.
In rare circumstances, urticaria can be the presenting feature of
hyperthyroidism. Rothfield9 reviewed 108 cases of
hyperthyroidism and found 2 cases of urticaria (1.85%) that varied with
the degree of hyperthyroidism. Pruritis was also found in a number of
patients, and severity varied along with thyroid state in 5 out of the
108 cases (4.63%).
The mechanism linking urticaria and hyperthyroidism is not clearly
understood. Chronic urticaria is thought to be triggered by activation
and degranulation of mast cells. Although IgG anti-thyroid
auto-antibodies do not directly activate mast cells, they are postulated
to make them more susceptible to activation by other
mediators10. In this case, thyroid peroxidase
antibodies were > 1000 iU/mL. Another proposed theory is
that IgE anti-TPO antibodies directly bind to mast cells to cause
autoallergic mast cell degranulation and activation11.
Furthermore, omalizumab, an anti-IgE therapy, provides particularly good
symptomatic improvement in patients with urticaria and positive IgE
anti-TPO antibodies12.
Treatment for hyperthyroidism consists of medications, surgery or
radioiodine. The currently licensed medications for hyperthyroidism
include carbimazole (converted to methimazole) and propylthiouracil,
both of which reduce the conversion of thyroxine (T4) to its active
form, triiodothyronine (T3)13,14. Specifically,
methimazole and propylthiouracil impede iodination of tyrosine residues
in thyroglobulin, an important step in conversion of T4 to T3.
Propylthiouracil also inhibits peripheral conversion of T4 to T3,
although the therapeutic effect of this is unclear13.
Carbimazole itself is also a known cause of rash and
urticaria15,16. A review of the yellow card scheme
between 1981 to 2003 found rashes to be the 4th most
common side effect for carbimazole, behind neutropenia, hepatobiliary
disorders and agranulocytosis17. Propylthiouracil, the
lesser used medication for hyperthyroidism, has a number of adverse
effects including urticaria and other skin reactions; skin eruptions
occur in 4-6% of patients18.
In patients that are otherwise clinically euthyroid, a suitable strategy
would be to withhold carbimazole (or propylthiouracil) when an
urticarial rash first develops. But the correct action in patients with
uncontrolled hyperthyroidism is less clear, as withholding anti-thyroid
drugs could result in an exacerbation of thyrotoxicosis and consequently
intensify the urticaria. In such patients, a trial period of
carbimazole-free therapy in order to closely assess urticarial response
would be justified. Talaprapta et al19 faced the above
dilemma in 2007, and opted to withhold carbimazole therapy, resulting in
an aggravated thyrotoxicosis with a persistent rash. They then found the
urticarial rash to improve once the patient’s hyperthyroid state had
resolved with propylthiouracil.
In our patient the hyperthyroidism developed shortly before urticaria,
although she was clinically euthyroid when she presented to hospital.
But despite the unremarkable FT4 level, it is likely that the IgE
anti-TPO cascade was still rampant as evidenced by the high anti-TPO
levels. Interestingly, the decision to stop carbimazole did result in
symptomatic relief however this coincided with high dose
anti-histamines.
In such patients where the true cause of urticaria is unclear
symptomatic relief can be sought while investigating with a
trial-and-error approach (see table 2) .
Consent: Written and verbal consent provided by patient for the
article and related images
Competing interests: None
Data Sharing: The data that support the findings of this study
are openly available in [repository name e.g “figshare”] at
http://doi.org/[doi], reference number [reference number].