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].