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Vitiligo, autoimmunity, and cancer?

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By Warren R. Heymann, MD
May 3, 2017

autoimmune thyroid disease
Disorders associated with autoimmune thyroid disease: systemic lupus erythematosus (A), progressive systemic sclerosis (B), bullous pemphigoid (C), pemphigus vulgaris (D), urticaria (E), and vitiligo (F).
Credit: JAAD
While attending the pre-AAD pediatric dermatology seminar in Orlando, I received a call from my college roommate in mid-afternoon. My close friends know not to call during working hours, unless it’s urgent — naturally, I get nervous when the caller ID reveals their identity. I stepped away from the lecture to learn that his son underwent a thyroidectomy for papillary thyroid cancer.

“How was it detected?” I inquired. “Did he have an ultrasound?”

“Yes, but after the internist just felt a nodule on a routine exam of his neck. He’s lucky he had a thorough exam.”

Fortunately, my friend’s son is doing well. It’s refreshing to hear a story that’s becoming obsolete — detecting cancer by old-fashioned palpation.

According to Nguyen et al: “Thyroid cancer is the most common malignancy of the endocrine system, representing 3.8% of all new cancer cases in the United States and is the ninth most common cancer overall. The American Cancer Society estimates that 62,450 people in the United States will be diagnosed with thyroid cancer in 2015, and 1950 deaths will result from the disease. Thyroid cancer is categorized into 4 main types – papillary (the most common and least aggressive), follicular (including the Hürthle cell carcinoma, being more aggressive than papillary carcinoma), medullary (calcitonin-producing and associated with multiple endocrine neoplasia 2), and anaplastic (manifested by early and widespread metastasis) (1).

The increased incidence of thyroid cancer can be analogized to the melanoma epidemic, with increased detection playing at least a partial role in the expanding number of cases. Imaging studies (ultrasounds, computed tomography, magnetic resonance imaging, and positron emission tomography scans) incidentally detect thyroid nodules.

Vitiligo is extraordinarily common, with a prevalence up to 2.16% of the world’s population. Extensive disease and increasing age are the factors that correlate most with vitiligo-associated autoimmune disease. Virtually every autoimmune disorder has been associated with vitiligo, but clearly, autoimmune thyroid disease (AITD, Graves and Hashimoto) lead the list. (Segmental vitiligo, representing about 15% of cases is not associated with AITD, compared to the majority non-segmental type) (2).

I have read innumerable studies about the association of AITD with vitiligo, that I tend to gloss over them. I was about to do the same with the paper by Bae et al, when my eye caught the conclusion: “Vitiligo was significantly associated with overt autoimmune thyroid diseases and overt thyroid cancer” (emphasis mine).

Utilizing the Korean National Health Insurance claims database, the authors enrolled 73,336 vitiligo patients and 146,672 age and sex-matched controls. Patients with vitiligo were at increased risks of Graves disease (odds ratio [OR] 2.610), Hashimoto thyroiditis (OR 1.609) and thyroid cancer (OR 1.127) compared with the controls. The associations were consistently stronger in males and younger patients. The authors acknowledge that one of the limitations of the study was that individual clinical information was not available (3).

This is worth exploring in greater detail before misinterpretation by the lay press, or going viral, causing anxious patients (and parents) with vitiligo to demand neck ultrasounds. It has been long known, but frequently forgotten, that Hashimoto thyroiditis may rarely be complicated by thyroid lymphoma (4). In a study of 580 thyroidectomies, 43 cases (7.4%) of incidental thyroid cancers (all papillary – 34 conventional and 9 follicular variants) were discovered and they were significantly associated with moderate-to-severe lymphocytic thyroiditis (5). Clearly, further research is necessary. In Bae’s study, it would have been valuable to know what the precise thyroid cancers were. Additionally, an odds ratio of 1.127 for the risk of thyroid cancer in vitiligo is not overwhelming. Although lymphocytic thyroiditis may be associated with thyroid lymphoma or papillary carcinoma, the former is rare and the latter likely incidental.

Many opinions abound regarding how to assess patients with vitiligo for associated autoimmune diseases. I think it is appropriate to inquire about a family history of thyroid and other autoimmune disorders, discuss the association of AITD (without too much emphasis on other autoimmune diseases, unless there is a pertinent family history), consider checking a TSH periodically and perhaps obtaining thyroid autoantibodies. My approach is flexible — I try to comfort the afflicted and afflict the comfortable. For patients absolutely convinced that they have associated illness, only checking all labs will mollify them. For those patients who think that they are immune to complications, I encourage them to at least check a TSH. As for the risk of thyroid cancer, until there is more data, I will not be routinely ordering thyroid ultrasounds. I might start palpating the gland though. You never know what you might find, whether it’s related to vitiligo, or not.

1. Nguyen QT, et al. Diagnosis and treatment of patients with thyroid cancer. Am Health Drug Benefits 2015; 8(1): 30–40.
2. Ezzedine K, Silverberg N. A practical approach to the diagnosis and treatment of vitiligo in children. Pediatrics 2016 138(1). pii: e20154126.
3. Bae JM, et al. Vitiligo and overt thyroid diseases: A nationwide population-based study in Korea. J Am Acad Dermatol 2017: 76: 871-8.
4. Chiang B, et al. Commonly forgotten complication of Hashimoto’s thyroiditis. BMJ Case Rep 2016; 2016. pii: bcr2016217568.
5. Farrell E, et al. Impact of lymphocytic thyroidisits on incidence of pathological incidental thyroid carcinoma. Head Neck 2017; 39: 122-7.

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