Q:

I have a 27 yr old female with chronic urticaria who has failed tx with high dose antihistamines, including doxepin and hydroxyzine--given to the point of intolerable sedation; H2 blockers, Singulair, but does respond temporarily to oral steroids--She tells me she is miserable and is very frustrated. She has a h/o Hashimoto's with an elevated TPO Ab but is clinically and biochemically euthryoid. She referenced several articles describing improvement of urticaria with thyroid replacement and wishes to pursue this tx. Her endocrinologist refused, fearing iatrogenic hyperthyroidism and asks if there is solid evidence in the allergy literature supporting this treatment. I saw several articles from a number of years ago claiming success, such as JACI Volume 96, Issue 6 , Pages 901-905, December 1995.

 

Is there solid evidence of the effectiveness of using Synthroid or some other form of thyroid replacement to treat urticaria in euthryoid patients with elevated anti-thyroid antibodies from a study with a larger number of patients?How would you treat this pt? Thanks, as always, for your expert advice

A:

Thank you for your recent inquiry.

Unfortunately there is no definitive answer to your question. The state of confusion regarding this issue was fairly recently assessed by the Academy in a survey sent to its members (1). From this survey, one can easily see that there is controversy and confusion related to the interpretation of the available literature in this area.

Perhaps the best literature regarding this topic has appeared in endocrinology publications. Presumably this is the case because endocrinologists are perhaps more interested in the effect of thyroid treatment in patients who are euthyroid. There is one paper dealing directly with this issue, and a second excellent review which mentions the problem. I have copied abstracts from both of these publications for your convenience below. As you can see, they discourage the use of thyroid treatment in patients with chronic urticaria who are euthyroid because of potential side effects and lack of high grade evidence that such treatment is effective.

Unfortunately the term "solid evidence" is oftentimes dependent upon the eyes of the beholder, but based upon the studies to date, I think that one would find it difficult to come to a consensus based upon the present evidence in favor of the administration of thyroid to euthyroid patients with chronic urticaria. Based upon my personal assessment of the literature, I probably would not use this agent, especially with an objection from an endocrinologist who was consulted.

Finally, in case you are interested in alternative therapy for your patient, there are two excellent references with David Khan as the senior author (2, 3) that summarize alternative therapies.

Thank you again for your inquiry and we hope this response is helpful to you.

Clin Exp Dermatol. 2010 Aug;35(6):603-7. Epub 2009 Oct 23.
Effect of levothyroxine treatment on clinical symptoms and serum cytokine levels in euthyroid patients with chronic idiopathic urticaria and thyroid autoimmunity.
Kiyici S, Gul OO, Baskan EB, Hacioglu S, Budak F, Erturk E, Imamoglu S.
Source
Department of Endocrinology and Metabolism, Medical Faculty, Uludag University, Bursa, 16059, Turkey. Abstract
Background: Screening for thyroid autoimmunity in patients with chronic idiopathic urticaria (CIU) is generally recommended. However, there are not yet sufficient data as to whether levothyroxine treatment is beneficial for the clinical symptoms of CIU in patients with thyroid autoimmunity.
Aim: We investigated the effect of levothyroxine treatment on clinical symptoms and serum tumour necrosis factor (TNF)-alpha, interleukin (IL)-10 and interferon (IFN)-gamma levels in euthyroid patients with CIU and thyroid autoimmunity.
Methods: In total, 15 patients with CIU and positive thyroid autoantibodies were randomized to receive either levothyroxine plus 5 mg/day desloratadine (suppression group, n = 8) or 5 mg/day desloratadine alone (control group, n = 7) for 12 weeks. Clinical symptoms of CIU, thyroid hormone levels, thyroid antibodies and serum cytokine levels were assessed at baseline and after the treatment.
Results:  There were significant improvements in pruritus score and severity of weals in both groups compared with baseline values, but when the two groups were compared, there was no significant difference in the patients' clinical symptoms. Thyroid antibody titres were not different according to intragroup and intergroup analysis. In the suppression group, serum IFN-gamma and TNF-alpha levels were increased after treatment with levothyroxine compared with baseline values and there was a borderline statistical significance (P = 0.05 for both).
Conclusions:  These results suggest that levothyroxine treatment is not a reasonable option in euthyroid patients with CIU and thyroid autoimmunity. Augmentation of cytokine production after levothyroxine treatment seems to be related to the immunomodulatory effects of TSH-suppressive treatment.
PMID:
19874329
[PubMed - indexed for MEDLINE]

Thyroid. 2011 Apr;21(4):401-10.
Urticaria and thyroid autoimmunity.
Bagnasco M, Minciullo PL, Saraceno GS, Gangemi S, Benvenga S.
Source
Terapia Medica e Radiometabolica, Dipartimento di Patologie Immunoendocrinologiche, Azienda Ospedaliera Universitaria San Martino, Genoa, Italy.
Abstract
Background: Chronic urticaria is a common clinical condition whose etiology, in about 75% of cases, is unknown and is therefore called chronic idiopathic urticaria (CIU). A link between CIU and autoimmune thyroid diseases was proposed several decades ago. Here we review this topic.
Summary:  Several studies have been performed to determine if and to what degree there is an association between CIU and autoimmune thyroid diseases, particularly autoimmune thyroiditis. Many of these studies were not well controlled, however. Approximately one-fourth of CIU patients have serological evidence of thyroid autoimmunity, suggesting that these two disorders are associated. The mechanisms for the apparent association between CIU and serological evidence of thyroid autoimmunity are not clear. There are no data regarding the correlations between CIU and histological features of autoimmune thyroiditis or hypothyroidism. Despite this, there are anecdotal reports regarding L-thyroxine administration in patients with CIU.
Conclusions:  Screening for thyroid autoimmunity is probably useful in patients with CIU. More solid evidence, based on still lacking well-conducted controlled studies, is desirable to determine if there is a therapeutic role for L-thyroxine treatment in ameliorating the skin manifestations of urticaria.

Reference:
1. Sheikh J, et al. A survey of allergists regarding the association of thyroid autoimmunity with chronic urticaria. J Allergy Clin Immunol 2009; 123(5):1173-1175.
2. Morgan M, Khan D. Therapeutic alternatives for chronic urticaria: an evidence-based review, Part 2. Ann Allergy Asthma Immunol 2008 (June); 100(6):517-526.
3. Morgan M. Khan D. Therapeutic alternatives for chronic urticaria: an evidence-based review, Part 1. Ann Allergy Asthma Immunol 2008; 100(5):403-412.

Sincerely,
Phil Lieberman, M.D.

AAAAI - American Academy of Allergy Asthma & Immunology