Pretibial Myxedema: Symptoms, Types, Causes and Treatment

Pretibial myxedema (PTM), also known as localized myxedema or thyroid dermopathy, is a rare skin manifestation most commonly associated with autoimmune thyroid diseases, especially Graves’ disease. Although it is not usually life-threatening, its physical and cosmetic effects can be distressing and, in severe cases, disabling. This article explores PTM in depth—how it appears, its various forms, why it occurs, and the current evidence-based approaches to management.

Symptoms of Pretibial Myxedema

Pretibial myxedema generally presents as changes in the skin of the lower legs, but the symptoms can range from subtle to dramatic. Recognizing these signs is crucial for early intervention and improved quality of life.

Symptom	Description	Frequency/Severity	Source(s)
Skin thickening	Firm, indurated plaques, mostly shins	Common, often progressive	2 3 7 9
Peau d’orange look	Orange-peel texture	Frequent in early lesions	2 3
Non-pitting edema	Swelling that doesn’t indent easily	Most classic presentation	2 3 6 7 9
Nodules	Localized, rubbery bumps	Occasional	6 11
Elephantiasis	Massive swelling, skin overgrowth	Rare, severe cases	7 13
Itching/Tenderness	Discomfort, itch, or pain	Variable	2 3 6
Color change	Brown, reddish, or orange hue	Sometimes noted	2 3 7
Pitting edema	Indentation with pressure	Rare, not typical	1

Table 1: Key Symptoms

Overview of Symptoms

The skin changes in PTM are often the first—and sometimes only—visible sign of the disease outside the thyroid gland. Symptoms may appear gradually or insidiously, and their severity can vary widely.

Skin Lesions and Texture

• Plaques and Thickening: The most common presentation is firm, raised plaques on the shins or feet. These plaques feel indurated (hardened) and may be brownish or orange in color, occasionally with a characteristic “peau d’orange” (orange peel) texture, caused by skin thickening and dimpling 2 3 7 9.
• Edema: Non-pitting edema (swelling that doesn’t leave an indentation when pressed) is the hallmark of PTM. Rarely, pitting edema may occur, typically due to other causes or unusual presentations 1.
• Nodules and Elephantiasis: Nodular lesions or, in severe cases, massive swelling and skin overgrowth (elephantiasis nostras verrucosa) can develop. These forms are rare but can lead to significant functional impairment 6 7 13.
• Itching and Discomfort: Patients may experience itching, tenderness, or even pain, but many cases are asymptomatic aside from cosmetic changes 2 6.
• Color Changes: The affected skin may take on a brown, orange, or reddish hue 2 3.

Association with Other Symptoms

• PTM commonly occurs alongside eye involvement (Graves’ ophthalmopathy) and may be associated with other signs of autoimmune thyroid disease. Systemic symptoms like sweating, palpitations, or shortness of breath are not due to PTM itself, but rather underlying thyroid dysfunction 1 9.

Types of Pretibial Myxedema

PTM is not a single entity but a spectrum of skin changes with several recognizable patterns. Understanding these types can help guide diagnosis and management.

Type	Main Features	Severity	Source(s)
Non-pitting	Firm, thickened plaques, non-indenting	Typical, mild	2 3 6 8 9
Plaque	Broad, raised, indurated areas	Moderate	2 3 6
Nodular	Discrete, rubbery nodules	Mild/self-limit	6 11
Elephantiasis	Severe, massive swelling, hyperkeratosis	Severe/rare	6 7 13
Diffuse	Widespread thickening, less raised	Variable	11
Pitting	Indents with pressure, more fluid-like	Rare/atypical	1

Table 2: Main Types of Pretibial Myxedema

Morphological Variants

Non-pitting (Classic) and Plaque Forms

• Non-pitting edema is the classic form: thickened, waxy plaques that do not indent with pressure, almost always located on the shins or feet 2 3 6 8 9.
• Plaque type features broad, raised, indurated areas. These may merge or remain discrete and are the most frequently observed 2 3 6.

Nodular and Diffuse Types

• Nodular PTM presents as localized, rubbery bumps. Interestingly, this form tends to be self-limited, with less tendency to progress or recur after remission 6 11.
• Diffuse form is characterized by more widespread thickening, sometimes merging with other forms 11.

Elephantiasis (Elephantiasic) Type

• The elephantiasis variant represents the most severe form, with massive swelling, overgrowth, and skin changes resembling chronic lymphedema. This can lead to immobility and disability if not managed aggressively 6 7 13.

Pitting Edema

• Pitting PTM is unusual. Unlike the classic form, this presents with swelling that leaves an indentation when pressed. It is often due to additional factors, such as vascular permeability or heart failure, rather than true PTM pathophysiology 1.

Evolution and Progression

• Lesions may evolve from one type to another, usually starting as non-pitting or plaque and, in rare instances, progressing to elephantiasis. Trauma or local pressure may trigger or worsen more severe variants 6 10.
• Severity and type often correlate with the level of thyroid-stimulating hormone receptor antibodies (TRAb) in the blood 6 10.

Causes of Pretibial Myxedema

The causes of PTM are complex and involve both autoimmune and local factors. Understanding the interplay between these elements sheds light on why only a subset of people with thyroid disease develop this skin condition.

Cause/Factor	Role in PTM	Notes/Correlation	Source(s)
TRAb (autoantibodies)	Stimulate fibroblasts, main cause	Strongest association	4 6 8 9 10
Graves’ disease	Underlying autoimmune disorder	Most common link	4 6 9 10
Hashimoto’s thyroiditis	Rarely associated	Less frequent	8 9
Local trauma	Triggers lesion development	Increases risk/relapse	6 10
Venous stasis/position	Promotes local changes	Standing/sitting roles	6 10
Cigarette smoking	Risk factor, worsens severity	Associated with relapse	5 6 10
Age	Older age increases risk	Minor effect	10
Mechanical factors	Localizes lesions to shins/feet	Dependent areas	9 10

Table 3: Main Causes and Risk Factors

Autoimmunity and Thyroid Disease

Autoantibodies and Fibroblast Activation

• The majority of PTM cases are linked to autoimmune thyroid disease, especially Graves’ disease 4 6 9 10.
• The main culprit is the thyroid-stimulating hormone receptor antibody (TRAb). These autoantibodies stimulate skin fibroblasts (the cells that produce connective tissue) to overproduce glycosaminoglycans, especially hyaluronic acid, which leads to mucinous swelling and skin changes 8 9 10.
• High TRAb levels correlate with severity and risk of relapse 6 10.

Other Thyroid Disorders

• Hashimoto’s thyroiditis and primary myxedema (hypothyroidism) rarely cause PTM, but it can occur 8 9.
• Occasionally, patients may have normal thyroid function (euthyroid), but still develop PTM due to autoimmune activity 4.

Local and Environmental Risk Factors

Trauma and Venous Stasis

• Local trauma (e.g., injury, pressure, scratching) and prolonged standing or sitting (venous stasis) are significant risk factors. These local factors can trigger lesion development or relapse, especially in the presence of elevated TRAb 6 10.
• The lower legs are most affected, partly due to gravity and pressure, which may explain the typical location of lesions 9 10.

Smoking and Age

• Cigarette smoking is a well-established risk factor, increasing both the likelihood and severity of PTM 5 6 10.
• Older individuals have a slightly increased risk, though age is a less influential factor than others 10.

Pathogenesis: Why the Shins?

• The exact reason for localization to the shins (pretibial area) is not entirely clear, but mechanical factors, local trauma, and dependent position (legs being lower than the heart) are thought to contribute 9 10.
• The process is both humoral (antibody-mediated) and cellular, involving immune activation of fibroblasts and infiltration of lymphocytes into the skin 6 8 9.

Treatment of Pretibial Myxedema

Although PTM is often mild and may resolve spontaneously, treatment can help reduce symptoms, improve appearance, and prevent progression, especially in severe cases. Several therapies are available, with varying degrees of evidence.

Treatment	Indication/Effectiveness	Notes	Source(s)
Topical corticosteroids	Mild-moderate, cosmetic improvement	Under occlusion preferred	2 9 12
Systemic corticosteroids	Severe/refractory cases	Mixed results, more side effects	9 11 14
Immunomodulators (IVIg/RTX)	Severe, progressive, or relapsed PTM	May improve both PTM and eye disease	5 11
Compression therapy	Significant edema/elephantiasis	Includes decongestive physiotherapy	9 13
Pentoxifylline	Adjunct for resistant cases	Combined with topical steroids	2
Local triiodothyronine	Rare, historical	May reduce lesion size	3
Observation	Asymptomatic/mild cases	Many remit spontaneously	9

Table 4: Main Treatment Approaches

First-Line and Supportive Therapies

Topical Corticosteroids

• Topical steroids under occlusive dressings (e.g., fluocinolone acetonide, clobetasol, triamcinolone) are the mainstay for mild-to-moderate PTM 2 9 12.
• Occlusion increases steroid penetration, leading to better results. Long-term use may be needed for maintenance 12.
• Many patients achieve significant cosmetic and symptomatic improvements.

Observation and Supportive Care

• Many mild cases, especially if asymptomatic, can be managed with observation alone—up to 50% of untreated mild cases remit over several years 9.
• Supportive measures include skin moisturization and avoiding trauma or prolonged standing.

Advanced Therapies

Systemic Corticosteroids

• Systemic (oral or injected) corticosteroids are reserved for more severe or refractory cases, but results are mixed and adverse effects can be significant 9 11 14.
• Not all patients respond, and relapses are common.

Immunomodulatory Therapies

• Intravenous immunoglobulin (IVIg) and rituximab (RTX) have shown benefits in severe or treatment-resistant PTM, leading to improvement or stabilization in most patients 5 11.
• These agents may also help with concurrent Graves’ ophthalmopathy, but optimal protocols remain under investigation.
• They are generally well tolerated but reserved for select, severe cases due to cost and potential side effects.

Compression and Decongestive Therapy

• Compression stockings, bandaging, and complete decongestive physiotherapy can provide significant relief in cases with marked edema or elephantiasis 9 13.
• In one reported case, intensive physiotherapy led to dramatic, sustained improvement in mobility and swelling 13.

Adjunctive and Experimental Treatments

• Pentoxifylline (a vasodilator/anti-inflammatory agent) may be helpful as an adjunct, especially in resistant cases, often combined with topical corticosteroids 2.
• Local injections of triiodothyronine (thyroid hormone) have been tried with some success in historical reports, but are rarely used today 3.

Prognosis and Relapse Prevention

• Early treatment of PTM, particularly before progression to severe forms, can help prevent complications 6.
• Reducing risk factors—such as smoking cessation, avoiding trauma, and managing thyroid function—is also important 10.
• Even with treatment, relapse can occur, especially if TRAb levels remain elevated or local risk factors persist 6 10.

Conclusion

Pretibial myxedema is a complex, visually striking, and sometimes debilitating complication of autoimmune thyroid disease. Its management requires a nuanced, individualized approach that considers both the underlying cause and the severity of skin changes.

Key takeaways:

• PTM most often presents as firm, non-pitting plaques or swelling of the shins, sometimes accompanied by itching or color change.
• Several types exist, ranging from mild nodular forms to severe elephantiasis.
• The main cause is autoimmunity—especially TRAb stimulating fibroblasts in the skin—but local factors (trauma, standing, smoking) also play a key role.
• Treatment depends on severity: topical corticosteroids under occlusion are first-line for most; immunomodulatory therapy and decongestive physiotherapy are reserved for severe or refractory cases.
• Many cases remit spontaneously, but relapse can occur if risk factors persist.

By understanding the symptoms, types, causes, and treatments of PTM, patients and clinicians can work together to reduce symptoms, improve quality of life, and prevent progression of this rare but impactful condition.