Subacute thyroiditis and influenza vaccine
Kaohsiung J Med Sci June 2006 • Vol 22 • No 6 297
Subacute thyroiditis (SAT) is a self-limiting thyroid disease associated with a triphasic clinical course of hyperthyroidism, hypothyroidism, and return to normal thyroid function. The well-known clinical features of SAT include thyroid pain with symptoms of hyperthyroidism, suppressed level of thyroid-stimulating hormone (TSH), low thyroid uptake of radioactive iodine, and elevated erythrocyte sedimentation rate [1,2]. Diagnosis is based on clinical and laboratory data, and tissue diagnosis is rarely required [1,3,4]. We present the case of a 25-year-old female with sudden onset of neck pain on the left side and swelling 2 days after she received an influenza vaccine injection of Vaxigrip®. Tracing back her history, she had experienced the same symptoms when she was 12 years old and recovered spontaneously. Therefore, we strongly suspected that SAT was possibly associated with influenza vaccine (Vaxigrip®) in this case.
S
UBACUTE
T
HYROIDITIS
F
OLLOWING
I
NFLUENZA
V
ACCINE
(V
AXIGRIP
®
)
IN
A
Y
OUNG
F
EMALE
Jeng-Yueh Hsiao, Shih-Chieh Hsin, Ming-Chia Hsieh, Pi-Jung Hsia, and Shyi-Jang Shin
Department of Endocrinology and Metabolism, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Subacute thyroiditis (SAT), also called de Quervain thyroiditis or granulomatous thyroiditis, is a self-limiting, possibly viral, and inflammatory thyroid disorder that is usually associated with thyroid pain and systemic symptoms. This report details a case of SAT possibly associated with influenza vaccine (Vaxigrip®) in a young female. The diagnosis, therapeutic management and outcome are
discussed.
Key Words: subacute thyroiditis, de Quervain thyroiditis, influenza vaccine (Kaohsiung J Med Sci 2006;22:297–300)
Received: August 10, 2005 Accepted: February 9, 2006 Address correspondence and reprint requests to: Dr Shyi-Jang Shin, Department of Endocrinology and Metabolism, Kaohsiung Medical University Chung-Ho Memorial Hospital, 100 Tzyou 1st Road,
Kaohsiung 807, Taiwan. E-mail: [email protected]
C
ASER
EPORTA 25-year-old female suffering from fever, left neck swelling, and tender bulging mass for 3 days visited our clinic. Her body temperature ranged from 37 to 39°C. There were no chills, sore throat, cough, shortness of breath or chest pain, and no genitourinary symptoms. Two days before this episode of fever and subsequent development of a small, tender bulging neck mass, which progressively enlarged, she had received influenza vaccine (Vaxigrip®). Tracing back her history, at 12 years of age, she had experienced a similar episode from which she recovered spontaneously, but she had not received any vaccination at that time.
On physical examination, her body temperature was 38°C, pulse rate was 90 bpm, respiratory rate was 15 breaths/ min, and blood pressure was 110/70 mmHg. Her sclera was anicteric, pharynx was noninjected, and neck was supple. There was no cervical lymphadenopathy. Heart sounds were regular without murmurs, rubs or gallops. Her breathing sounds were clear. There was no skin rash and neurologic examination results were normal. A chest radiograph showed normal results.
Routine laboratory tests were unremarkable except for an erythrocyte sedimentation rate of 53 mm/hour (normal, 0–10 mm/hour). The leukocyte count was 9,790/μL (normal,
J.Y. Hsiao, S.C. Hsin, M.C. Hsieh, et al
298 Kaohsiung J Med Sci June 2006 • Vol 22 • No 6
4,000–11,000/μL) and C-reactive protein level was 14 μg/ mL (normal, < 5 μg/mL). Urinalysis showed normal results. Blood culture results were negative. Thyroid function test results were normal (total T4, 8.2 μg/dL; total T3, 85 ng/dL; TSH, 1.0 μU/mL). Microsomal and thyroglobulin anti-body test results were negative. Thyroid echocardiography showed a hypoechogenic area over the left lobe (Figure 1). Multinuclear giant cell granulomas were observed in a fine-needle aspiration biopsy of the thyroid (Figure 2). The patient became afebrile during the next week, while receiv-ing nonsteroidal anti-inflammatory drugs and steroids and recovered 2 weeks later. The tender neck mass also disappeared. According to the clinical manifestations, SAT was diagnosed. Since there was no viral infection prior to this episode and fever had occurred just after influenza vaccination, we suspected that this episode of SAT was associated with the administration of influenza vaccine.
D
ISCUSSIONSAT has been termed granulomatous giant cell or de Quervain’s thyroiditis. It is characterized by a generally self-limiting, usually painful inflammatory lesion of the thyroid gland, most probably of viral origin [5]. Many viruses have been implicated, including mumps, Coxsackie, influenza, adenoviruses, and echoviruses [6–8]. All current evidence indicate that SAT is not an autoimmune disease. The peak incidence occurs at 30–50 years of age, and women are affected thrice more frequently than men [3,9].
SAT begins with a prodrome of generalized myalgias, pharyngitis, low-grade fever and fatigue. Patients then present with fever and severe neck pain, swelling, or both. Painful SAT, which is a self-limiting inflammatory disor-der, is the most common cause of thyroid pain [10]. A viral cause of SAT has, therefore, been proposed, but clear evi-dence is still lacking [7].
The hallmark of painful SAT is a markedly elevated erythrocyte sedimentation rate. C-reactive protein con-centration is similarly elevated [11]. Color-flow Doppler ultrasonography may also help to make this distinction; in patients with Graves’ disease, the thyroid gland is hyper-vascular, whereas in patients with painful SAT, the gland is hypoechogenic and has low-to-normal vascularity [12]. The treatment for painful SAT is to provide symptom-atic relief only. Nonsteroidal medications or salicylates are adequate to control mild thyroid pain; high doses of glucocorticoids (e.g. 40 mg/day prednisone) provide immediate relief. The doses of steroid should be tapered over a period of 4–6 weeks [13].
SAT, which is considered to be a viral disease [6–8], rarely recurs after a complete recovery, possibly because of immunity to the offending virus. However, late recurrence after several years has been reported [14–17]. The recurrent episodes were similar to the first episode of SAT. The titers of various viral antibodies were not increased during the clinical course of recurrence [17].
If vaccination is performed with heterologous antigens that are sufficiently different to permit an immunologic response, but are sufficiently similar to react with autologous antigens, then the vaccinated antigen may induce various immune response and systemic symptoms such as fever and myalgia. We report in this case that SAT occurred just after influenza vaccination and without a recent episode of viral infection before SAT. The patient had experienced a similar episode of fever and tender neck mass at 12 years of age, so SAT could be a possible diagnosis for that episode.
Figure 1. Thyroid ultrasonography showed a hypoechogenic area over the left lobe of the thyroid gland (arrow).
Figure 2. Subacute thyroiditis: multinuclear giant cell granulomas were observed in a fine-needle aspiration biopsy of the thyroid (arrow) (Liu stain, 100×).
Subacute thyroiditis and influenza vaccine
Kaohsiung J Med Sci June 2006 • Vol 22 • No 6 299
The recurrent episode is thought possibly to have been induced by the influenza vaccine injection due to delayed hypersensitivity reactions with sensitized lymph-oid cells.
The side effects of and adverse reactions to influenza vaccine (Vaxigrip®) [18,19] that occurred during clinical trials were erythema, redness, swelling, pain, ecchymosis and induration. The most frequent side effect of vaccination is soreness at the vaccination site (affecting 10–64% patients) that lasts < 2 days. Systemic reactions included fever, malaise, myalgia, headache, shivering, sweating, muscular pain and joint pain. These reactions begin 6–12 hours after vaccination and can persist for 1–2 days. No clinical case report to date has demonstrated an association between SAT and influenza vaccination.
In the Minnesota cohort study [20], the inclusion criteria for diagnosis of SAT were any one of the following: (1) painful thyroid and either suppressed uptake of 131I or elevated erythrocyte sedimentation rate, or both; (2) unilateral thyroid pain with abnormally low uptake of 131I and elevated erythrocyte sedimentation rate; and (3) pathologic diagnosis (surgical specimen or biopsy). In our case, the patient presented with fever, left neck swelling, and tender bulging mass. In addition, markedly elevated erythrocyte sedimentation rate was observed. These findings were consistent with a diagnosis of SAT. As there was no evidence of recent bacterial or viral infection prior to this episode and because fever had occurred just after influenza vaccination, we highly suspected this episode of SAT to be directly associated with the influenza vaccine or that the recurrence was aggravated by influenza vaccination, but more precise methods are required to determine this possibility.
This case was a rare clinical case. Other researchers [21, 22] compiled and analyzed safety data on the inactivated split influenza vaccine, Vaxigrip®, from 28 clinical trials (total: 4,599 subjects aged 6 months to 99 years) to provide a robust estimate of the reactogenicity profile. The most frequent solicited reactions were nonsevere injection site pain and erythema in children, adults and the elderly. Mild or moderate fever was the most frequent reaction among 6- to 36-month-old individuals; few systemic reactions were reported in older groups. Reactogenicity was comparable in healthy and high-risk children. The long-term experience with the world’s most widely used influenza vaccine, Vaxigrip®, confirms its excellent tolerability, and its continued use in clinical practice worldwide is supported.
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