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Painless nodules on legs
A 34-YEAR-OLD MAN presented with a 6-month history of asymptomatic, progressively enlarging subcutaneous nodules over his bilateral lower legs. He denied any history of injury, and there was no bleeding or discharge. The patient had a history of Graves disease that had been treated with radioiodine therapy 2 years prior, followed by thyroxine replacement (150 mcg/d, 5 d/wk and 125 mcg/d, 2 d/wk). At the time of presentation, his thyroid function tests indicated subclinical hypothyroidism: free T4, 21.2 pmol/L (normal range, 11.8-24.6 pmol/L) and thyroid-stimulating hormone (TSH), 14.07 mIU/L (normal range, 0.27-4.2 mIU/L).
Examination revealed nontender, soft brown nodules over the bilateral shins, with minimal overlying lichenification (FIGURE 1). There was no peau d’orange (orange peel) appearance to suggest significant edema. A punch biopsy was performed.
WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?
Diagnosis: Pretibial myxedema
The patient’s history, paired with the results of the punch biopsy, were consistent with a diagnosis of pretibial myxedema, part of the triad of Graves disease along with thyroid ophthalmopathy and acropachy (soft-tissue swelling of the hands and clubbing of the fingers). Histopathologic findings revealed wide separation of collagen bundles throughout the entire reticular dermis without fibroplasia (FIGURE 2A). The spaces contained basophilic strands (FIGURE 2B), and the strands stained strongly positive on Alcian blue (FIGURE 2C), confirming the presence of dermal mucin. Widely separated collagen fibers and deposited mucin are indicative of pretibial myxedema. No granulomas or lymphoid proliferations were seen.
The pathogenesis of pretibial myxedema is widely postulated to be due to the stimulation of dermal fibroblasts by anti–TSH antibodies, causing overproduction of glycosaminoglycans and hyaluronic acid1 and obstructing lymphatic microcirculation, resulting in nonpitting edema.2
There are 5 distinct clinical variants of pretibial myxedema1,3:
- The diffuse form is the most common. It manifests on the lower leg with hard, nonpitting edema and cutaneous thickening.
- The plaque form manifests on the lower leg as well-demarcated erythematous or pigmented flat-topped lesions.
- The nodular form, which our patient had, typically manifests on the lower leg as well-demarcated erythematous, pigmented, or skin-colored raised, solid lesions. There may be 1 lesion or several.
- The mixed form manifests as 2 or more of the other variants.
- The elephantiasic form is the rarest and the most severe. There are widespread swollen nodules and plaques on the lower legs and/or arms.
A rare, late manifestation
Although pathognomonic for Graves disease, pretibial myxedema is a late manifestation that occurs in less than 5% of these patients.4 The most common site of involvement is the pretibial region, although less common sites include the face, arms, shoulders, abdomen, pinna, and the location of previous scars.4
While pretibial myxedema usually is associated with hyperthyroidism, it can occur after treatment (as was the case here), while the patient is in a euthyroid or hypothyroid state. Radioiodine therapy has been reported to be a trigger for pretibial myxedema in 1 case report, although the pathophysiology is not fully understood.5
Continue to: More serious conditions must be ruled out
More serious conditions must be ruled out
The differential for painless nodules includes cutaneous lymphoma and atypical infections of fungal or mycobacterial etiology.
Cutaneous lymphoma that manifests with leg tumors includes primary cutaneous anaplastic CD30+ large cell lymphoma (PCALCL) and primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBL-LT). The former may occur in young patients, whereas the latter tends to manifest in the elderly. Biopsy shows a neoplastic proliferation of atypical lymphocytes within the dermis,6 differing from our case.
Atypical infections may be detected through bacterial, mycobacterial, or fungal cultures, and may be accompanied by elevated inflammatory markers or other systemic symptoms of the infection, setting it apart from pretibial myxedema.
Treatment is simple and noninvasive
Pretibial myxedema is usually asymptomatic, with minimal morbidity. The nodular variant may resolve spontaneously; thus, therapeutic management often is reserved for severe cases or for those with cosmetic concerns. Treatment options include mid- to high-potency topical corticosteroids with an occlusive dressing for 1 to 2 weeks (or until resolution) or an intralesional triamcinolone injection (5-10 mg/mL, single or monthly until resolution), compression stockings, and pneumatic compression.2
This patient was treated with a single intralesional injection of triamcinolone 10 mg/mL. The nodules resolved within a month.
1. Thammarucha S, Sudtikoonaseth P. Nodular pretibial myxedema with Graves’ disease: a case report. Thai J Dermatol. 2021;37:30-36.
2. Singla M, Gupta A. Nodular thyroid dermopathy: not a hallmark of Graves’ disease. Am J Med. 2019;132:e521-e522. doi: 10.1016/j.amjmed.2018.11.004
3. Lan C, Wang Y, Zeng X, et al. Morphological diversity of pretibial myxedema and its mechanism of evolving process and outcome: a retrospective study of 216 cases. J Thyroid Res. 2016:2016:265217
4. doi: 10.1155/2016/2652174 4. Patil MM, Kamalanathan S, Sahoo J, et al. Pretibial myxedema. QJM. 2015;108:985. doi: 10.1093/qjmed/hcv136
5. Harvey RD, Metcalfe RA, Morteo C, et al. Acute pre-tibial myxoedema following radioiodine therapy for thyrotoxic Graves’ disease. Clin Endocrinol (Oxf). 1995;42:657-660. doi: 10.1111/j.1365-2265.1995.tb02695.x
6. Schukow C, Ahmed A. Dermatopathology, cutaneous lymphomas. StatPearls [Internet]. Updated February 16, 2023. Accessed October 23, 2023. www.ncbi.nlm.nih.gov/books/NBK589703/
A 34-YEAR-OLD MAN presented with a 6-month history of asymptomatic, progressively enlarging subcutaneous nodules over his bilateral lower legs. He denied any history of injury, and there was no bleeding or discharge. The patient had a history of Graves disease that had been treated with radioiodine therapy 2 years prior, followed by thyroxine replacement (150 mcg/d, 5 d/wk and 125 mcg/d, 2 d/wk). At the time of presentation, his thyroid function tests indicated subclinical hypothyroidism: free T4, 21.2 pmol/L (normal range, 11.8-24.6 pmol/L) and thyroid-stimulating hormone (TSH), 14.07 mIU/L (normal range, 0.27-4.2 mIU/L).
Examination revealed nontender, soft brown nodules over the bilateral shins, with minimal overlying lichenification (FIGURE 1). There was no peau d’orange (orange peel) appearance to suggest significant edema. A punch biopsy was performed.
WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?
Diagnosis: Pretibial myxedema
The patient’s history, paired with the results of the punch biopsy, were consistent with a diagnosis of pretibial myxedema, part of the triad of Graves disease along with thyroid ophthalmopathy and acropachy (soft-tissue swelling of the hands and clubbing of the fingers). Histopathologic findings revealed wide separation of collagen bundles throughout the entire reticular dermis without fibroplasia (FIGURE 2A). The spaces contained basophilic strands (FIGURE 2B), and the strands stained strongly positive on Alcian blue (FIGURE 2C), confirming the presence of dermal mucin. Widely separated collagen fibers and deposited mucin are indicative of pretibial myxedema. No granulomas or lymphoid proliferations were seen.
The pathogenesis of pretibial myxedema is widely postulated to be due to the stimulation of dermal fibroblasts by anti–TSH antibodies, causing overproduction of glycosaminoglycans and hyaluronic acid1 and obstructing lymphatic microcirculation, resulting in nonpitting edema.2
There are 5 distinct clinical variants of pretibial myxedema1,3:
- The diffuse form is the most common. It manifests on the lower leg with hard, nonpitting edema and cutaneous thickening.
- The plaque form manifests on the lower leg as well-demarcated erythematous or pigmented flat-topped lesions.
- The nodular form, which our patient had, typically manifests on the lower leg as well-demarcated erythematous, pigmented, or skin-colored raised, solid lesions. There may be 1 lesion or several.
- The mixed form manifests as 2 or more of the other variants.
- The elephantiasic form is the rarest and the most severe. There are widespread swollen nodules and plaques on the lower legs and/or arms.
A rare, late manifestation
Although pathognomonic for Graves disease, pretibial myxedema is a late manifestation that occurs in less than 5% of these patients.4 The most common site of involvement is the pretibial region, although less common sites include the face, arms, shoulders, abdomen, pinna, and the location of previous scars.4
While pretibial myxedema usually is associated with hyperthyroidism, it can occur after treatment (as was the case here), while the patient is in a euthyroid or hypothyroid state. Radioiodine therapy has been reported to be a trigger for pretibial myxedema in 1 case report, although the pathophysiology is not fully understood.5
Continue to: More serious conditions must be ruled out
More serious conditions must be ruled out
The differential for painless nodules includes cutaneous lymphoma and atypical infections of fungal or mycobacterial etiology.
Cutaneous lymphoma that manifests with leg tumors includes primary cutaneous anaplastic CD30+ large cell lymphoma (PCALCL) and primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBL-LT). The former may occur in young patients, whereas the latter tends to manifest in the elderly. Biopsy shows a neoplastic proliferation of atypical lymphocytes within the dermis,6 differing from our case.
Atypical infections may be detected through bacterial, mycobacterial, or fungal cultures, and may be accompanied by elevated inflammatory markers or other systemic symptoms of the infection, setting it apart from pretibial myxedema.
Treatment is simple and noninvasive
Pretibial myxedema is usually asymptomatic, with minimal morbidity. The nodular variant may resolve spontaneously; thus, therapeutic management often is reserved for severe cases or for those with cosmetic concerns. Treatment options include mid- to high-potency topical corticosteroids with an occlusive dressing for 1 to 2 weeks (or until resolution) or an intralesional triamcinolone injection (5-10 mg/mL, single or monthly until resolution), compression stockings, and pneumatic compression.2
This patient was treated with a single intralesional injection of triamcinolone 10 mg/mL. The nodules resolved within a month.
A 34-YEAR-OLD MAN presented with a 6-month history of asymptomatic, progressively enlarging subcutaneous nodules over his bilateral lower legs. He denied any history of injury, and there was no bleeding or discharge. The patient had a history of Graves disease that had been treated with radioiodine therapy 2 years prior, followed by thyroxine replacement (150 mcg/d, 5 d/wk and 125 mcg/d, 2 d/wk). At the time of presentation, his thyroid function tests indicated subclinical hypothyroidism: free T4, 21.2 pmol/L (normal range, 11.8-24.6 pmol/L) and thyroid-stimulating hormone (TSH), 14.07 mIU/L (normal range, 0.27-4.2 mIU/L).
Examination revealed nontender, soft brown nodules over the bilateral shins, with minimal overlying lichenification (FIGURE 1). There was no peau d’orange (orange peel) appearance to suggest significant edema. A punch biopsy was performed.
WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?
Diagnosis: Pretibial myxedema
The patient’s history, paired with the results of the punch biopsy, were consistent with a diagnosis of pretibial myxedema, part of the triad of Graves disease along with thyroid ophthalmopathy and acropachy (soft-tissue swelling of the hands and clubbing of the fingers). Histopathologic findings revealed wide separation of collagen bundles throughout the entire reticular dermis without fibroplasia (FIGURE 2A). The spaces contained basophilic strands (FIGURE 2B), and the strands stained strongly positive on Alcian blue (FIGURE 2C), confirming the presence of dermal mucin. Widely separated collagen fibers and deposited mucin are indicative of pretibial myxedema. No granulomas or lymphoid proliferations were seen.
The pathogenesis of pretibial myxedema is widely postulated to be due to the stimulation of dermal fibroblasts by anti–TSH antibodies, causing overproduction of glycosaminoglycans and hyaluronic acid1 and obstructing lymphatic microcirculation, resulting in nonpitting edema.2
There are 5 distinct clinical variants of pretibial myxedema1,3:
- The diffuse form is the most common. It manifests on the lower leg with hard, nonpitting edema and cutaneous thickening.
- The plaque form manifests on the lower leg as well-demarcated erythematous or pigmented flat-topped lesions.
- The nodular form, which our patient had, typically manifests on the lower leg as well-demarcated erythematous, pigmented, or skin-colored raised, solid lesions. There may be 1 lesion or several.
- The mixed form manifests as 2 or more of the other variants.
- The elephantiasic form is the rarest and the most severe. There are widespread swollen nodules and plaques on the lower legs and/or arms.
A rare, late manifestation
Although pathognomonic for Graves disease, pretibial myxedema is a late manifestation that occurs in less than 5% of these patients.4 The most common site of involvement is the pretibial region, although less common sites include the face, arms, shoulders, abdomen, pinna, and the location of previous scars.4
While pretibial myxedema usually is associated with hyperthyroidism, it can occur after treatment (as was the case here), while the patient is in a euthyroid or hypothyroid state. Radioiodine therapy has been reported to be a trigger for pretibial myxedema in 1 case report, although the pathophysiology is not fully understood.5
Continue to: More serious conditions must be ruled out
More serious conditions must be ruled out
The differential for painless nodules includes cutaneous lymphoma and atypical infections of fungal or mycobacterial etiology.
Cutaneous lymphoma that manifests with leg tumors includes primary cutaneous anaplastic CD30+ large cell lymphoma (PCALCL) and primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBL-LT). The former may occur in young patients, whereas the latter tends to manifest in the elderly. Biopsy shows a neoplastic proliferation of atypical lymphocytes within the dermis,6 differing from our case.
Atypical infections may be detected through bacterial, mycobacterial, or fungal cultures, and may be accompanied by elevated inflammatory markers or other systemic symptoms of the infection, setting it apart from pretibial myxedema.
Treatment is simple and noninvasive
Pretibial myxedema is usually asymptomatic, with minimal morbidity. The nodular variant may resolve spontaneously; thus, therapeutic management often is reserved for severe cases or for those with cosmetic concerns. Treatment options include mid- to high-potency topical corticosteroids with an occlusive dressing for 1 to 2 weeks (or until resolution) or an intralesional triamcinolone injection (5-10 mg/mL, single or monthly until resolution), compression stockings, and pneumatic compression.2
This patient was treated with a single intralesional injection of triamcinolone 10 mg/mL. The nodules resolved within a month.
1. Thammarucha S, Sudtikoonaseth P. Nodular pretibial myxedema with Graves’ disease: a case report. Thai J Dermatol. 2021;37:30-36.
2. Singla M, Gupta A. Nodular thyroid dermopathy: not a hallmark of Graves’ disease. Am J Med. 2019;132:e521-e522. doi: 10.1016/j.amjmed.2018.11.004
3. Lan C, Wang Y, Zeng X, et al. Morphological diversity of pretibial myxedema and its mechanism of evolving process and outcome: a retrospective study of 216 cases. J Thyroid Res. 2016:2016:265217
4. doi: 10.1155/2016/2652174 4. Patil MM, Kamalanathan S, Sahoo J, et al. Pretibial myxedema. QJM. 2015;108:985. doi: 10.1093/qjmed/hcv136
5. Harvey RD, Metcalfe RA, Morteo C, et al. Acute pre-tibial myxoedema following radioiodine therapy for thyrotoxic Graves’ disease. Clin Endocrinol (Oxf). 1995;42:657-660. doi: 10.1111/j.1365-2265.1995.tb02695.x
6. Schukow C, Ahmed A. Dermatopathology, cutaneous lymphomas. StatPearls [Internet]. Updated February 16, 2023. Accessed October 23, 2023. www.ncbi.nlm.nih.gov/books/NBK589703/
1. Thammarucha S, Sudtikoonaseth P. Nodular pretibial myxedema with Graves’ disease: a case report. Thai J Dermatol. 2021;37:30-36.
2. Singla M, Gupta A. Nodular thyroid dermopathy: not a hallmark of Graves’ disease. Am J Med. 2019;132:e521-e522. doi: 10.1016/j.amjmed.2018.11.004
3. Lan C, Wang Y, Zeng X, et al. Morphological diversity of pretibial myxedema and its mechanism of evolving process and outcome: a retrospective study of 216 cases. J Thyroid Res. 2016:2016:265217
4. doi: 10.1155/2016/2652174 4. Patil MM, Kamalanathan S, Sahoo J, et al. Pretibial myxedema. QJM. 2015;108:985. doi: 10.1093/qjmed/hcv136
5. Harvey RD, Metcalfe RA, Morteo C, et al. Acute pre-tibial myxoedema following radioiodine therapy for thyrotoxic Graves’ disease. Clin Endocrinol (Oxf). 1995;42:657-660. doi: 10.1111/j.1365-2265.1995.tb02695.x
6. Schukow C, Ahmed A. Dermatopathology, cutaneous lymphomas. StatPearls [Internet]. Updated February 16, 2023. Accessed October 23, 2023. www.ncbi.nlm.nih.gov/books/NBK589703/
