Acute diffuse facial edema as the first clinically recognized manifestation of Hashimoto’s thyroiditis: A case report

Introduction

Hashimoto’s thyroiditis is the most common cause of hypothyroidism and is a chronic autoimmune disorder characterized by lymphocytic infiltration and immune-mediated destruction of the thyroid gland. ¹ Patients often present with nonspecific systemic symptoms, including fatigue, constipation, cold intolerance, weight gain, and dry skin. ¹ Myxedema is a classic cutaneous manifestation of hypothyroidism and is more likely to develop in the setting of longstanding disease. ² It typically presents as nonpitting edema involving the face, pretibial, or periorbital regions. ² In some patients, however, cutaneous manifestations may precede the recognition of thyroid dysfunction and may be misinterpreted as other causes of localized swelling. Herein, we report a case of acute diffuse facial edema as the first clinically recognized manifestation of Hashimoto’s thyroiditis.

Case presentation

A previously healthy woman in her 20s presented with acute facial edema that had developed 1 day prior to presentation. She attended the dermatology clinic of Shengjing Hospital of China Medical University, Shenyang, China, in mid-2018. She reported mild facial pruritus without associated pain. She had not sought medical care elsewhere and had not taken any medications before presentation. Her medical, surgical, allergy, travel, and medication histories were unremarkable, and her family history was noncontributory. Upon further questioning, she reported a 6-month history of constipation and cold intolerance but denied headaches, fatigue, lethargy, weight gain, voice changes, or joint pain. Physical examination revealed a pale face with striking, diffuse, nonpitting edema involving the entire face, including the periorbital region, but sparing the lips (Figure 1). The swelling was nontender. No erythema or urticarial lesions were observed on the face or elsewhere on the body. There was no edema on the extremities, hands, or feet. The patient’s general condition and mental status were unremarkable. She walked into the clinic unaided and responded fluently and appropriately during the consultation. Her vital signs were stable, with a blood pressure of 89/60 mmHg, a pulse of 72 beats/min, and no fever. Laboratory investigations, including urinalysis, complete blood count, liver and kidney function tests, and serum immunoglobulin E (IgE) levels, were all within normal limits.

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Figure 1.

Diffuse nonpitting facial edema at initial presentation.

However, thyroid function tests showed a markedly elevated thyroid-stimulating hormone (TSH) (TSH >100.000 µIU/mL; reference range: 0.30–4.80) and reduced free thyroxine (FT4) (FT4 <5.15 pmol/L; reference: 9.01–19.05). Anti–thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg) antibody levels were both significantly elevated (>1000 IU/mL; reference ranges: anti-TPO, 0–5.61; anti-Tg, 0–4.11). Selected laboratory findings are summarized in Table 1. Thyroid ultrasound revealed an enlarged gland with diffusely reduced echogenicity. The patient was subsequently referred to the endocrinology department.

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Table 1.

Selected laboratory findings supporting the diagnosis and differential diagnosis before treatment and 1 month after initiation of levothyroxine therapy.

Category	Parameter	Before treatment	1 month after treatment	Reference range	Unit
Complete blood count	White blood cell count (WBC)	6.29	—	3.5–9.7	×10⁹/L
	Absolute eosinophil count (EO#)	0.11	—	0.04–0.49	×10⁹/L
	Hemoglobin (HGB)	117	—	110–150	g/L
	Platelet count (PLT)	221	—	135–350	×10⁹/L
Urinalysis	Urinary protein (PRO)	Negative	—	Negative	g/L
Liver and renal function	Total protein (TP)	76.1	—	60–83	g/L
	Albumin	48.7	—	35–53	g/L
	Creatinine	83.8	—	45–84	μmol/L
Total IgE	IgE	86.71	—	<100	IU/mL
Thyroid function	FT3	1.81	4.85	2.63–5.71	pmol/L
	FT4	<5.15	15.03	9.01–19.05	pmol/L
	TSH	>100	3.99	0.30–4.80	μIU/mL
Thyroid autoantibodies	Anti-TPO Ab	>1000	>1000	0–5.61	IU/mL
	Anti-Tg Ab	>1000	>1000	0–4.11	IU/mL

Values outside the reference range are presented in bold.

IgE: immunoglobulin E, FT3: free triiodothyronine, FT4: free thyroxine; TSH: thyroid-stimulating hormone; anti-TPO Ab: anti–thyroid peroxidase antibody; Anti-Tg Ab: anti-thyroglobulin antibody.

The markedly elevated TSH and low FT4 levels were consistent with primary hypothyroidism, whereas the significantly elevated anti-TPO and anti-Tg antibody levels supported the diagnosis of Hashimoto’s thyroiditis. The patient was initiated on levothyroxine replacement therapy at 25 µg/day, which was gradually increased to 75 µg/day. Facial edema improved markedly within 5 days of treatment initiation (Figure 2), and a euthyroid state was achieved within 1 month. No adverse events or complications were observed during treatment.

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Figure 2.

Marked improvement of facial edema on day 5 after initiation of levothyroxine therapy.

This case report was prepared in accordance with the Case Report (CARE) guidelines. ³ Written informed consent for treatment and publication was obtained from the patient. All patient information has been deidentified.

Discussion

Myxedema refers to the characteristic changes of the skin and subcutaneous tissues observed in patients with severe hypothyroidism and has been reported infrequently in clinical practice.^4–6 Approximately 10% of cases of myxedema occur in patients with hypothyroidism, particularly in the setting of autoimmune thyroid disease. ² Although xerosis is the most common cutaneous finding in hypothyroidism, generalized myxedema is traditionally considered its classic dermatologic manifestation. ⁷ Myxedema typically presents as nonpitting edema and may involve the pretibial, periorbital, facial, or acral regions. Characteristic facial features include periorbital puffiness, macroglossia, thickened lips, and broadening of the nose.^2,8

Unlike classic hypothyroid myxedema, which typically develops in the setting of longstanding hypothyroidism, ² our patient presented with sudden onset of diffuse facial edema as the first clinically recognized manifestation of hypothyroidism, without generalized involvement or the typical facial features of myxedema. To the best of our knowledge, only a few similar cases have been reported in the literature.^5,6,9 A comparable case of facial edema has been reported, with more prominent periorbital and upper-lip swelling. ⁶ Acute diffuse facial edema as the presenting manifestation of hypothyroidism can easily be misdiagnosed as angioedema or allergic reactions, thereby posing a diagnostic challenge, particularly when patients initially present to dermatology clinics.

Angioedema was considered the most important differential diagnosis because it presents as transient localized swelling and is often drug-induced, particularly by angiotensin-converting enzyme inhibitors, and may be accompanied by urticaria. ¹⁰ However, our patient had no relevant medication history, and the absence of erythema, warmth, or tenderness made infectious or allergic causes (e.g. erysipelas or contact dermatitis) less likely. Additionally, nephrotic syndrome, hypoproteinemia, and lymphedema ¹¹ were excluded based on normal laboratory findings and the clinical context at presentation.

Myxedema results from the accumulation of glycosaminoglycans in the dermis. Histologically, the dermis appears edematous, with mucin deposition separating connective tissue fibers. ⁴ In contrast to pretibial myxedema associated with hyperthyroidism, myxedema in hypothyroidism typically shows normal or inactive dermal fibroblasts without significant fibroblast proliferation. These glycosaminoglycan–protein complexes have a remarkable capacity to bind water and may expand up to 1000 times their original volume, resulting in dermal fluid retention and the characteristic nonpitting edema.^2,12 The exact pathophysiology remains unclear; however, mucopolysaccharide deposition may be related to markedly reduced thyroid hormone levels^7,13 or to prolonged stimulation of fibroblasts by TSH, analogous to fibroblast activation mediated by TSH-receptor antibodies in Graves’ dermopathy.^2,6,12

This report is limited by its single-case nature, and reporting of additional cases is warranted to better characterize acute diffuse facial edema as a presentation of hypothyroidism.

Conclusion

Acute diffuse facial edema associated with hypothyroidism may mimic conditions such as angioedema or allergic reactions, leading to diagnostic uncertainty. Thyroid function testing should therefore be considered in patients presenting with unexplained localized swelling.