Obesity-Associated Lymphedematous Mucinosis: An Emerging Variant of Pretibial Mucinosis – A Case Report and Literature Review

Abstract

Introduction

Obesity-associated lymphedematous mucinosis (OALM) is a rare variant of pretibial mucinosis linked to chronic lymphatic stasis in obesity. Because of its rarity, the condition may be underdiagnosed.

Case Presentation

An elderly obese woman presented with asymptomatic, erythematous to brownish pretibial plaques and nodules with bilateral leg edema. Thyroid dysfunction and other causes of edema were excluded. Skin biopsy revealed abundant dermal mucin with increased fibroblasts and lymphedema, confirming a diagnosis of OALM. Weight reduction and compression therapy were advised, but the patient was lost to follow-up. The pathogenesis of OALM is believed to involve local hypoxia from lymphatic stasis, resulting in excess mucin production. Lymphedema associated with obesity may demonstrate normal lymphoscintigraphy findings, and its pathogenesis remains unclear. Recognition of OALM is essential to differentiate it from pretibial myxedema and other causes of mucinosis.

Conclusion

OALM is a benign but likely under-recognized condition. It should be included in the differential diagnosis of pretibial mucinosis in obese patients, with histopathology playing a crucial role in diagnosis.

Introduction

Cutaneous mucinoses are a group of disorders marked by excessive accumulation of mucin within the skin. They are classified into two categories: primary cutaneous mucinoses, in which the mucin deposition is the main histopathological feature and central to disease manifestation, and secondary mucinoses, where mucin accumulation occurs in association with other cutaneous or systemic disorders [1]. Cutaneous mucinoses may also be classified as localized or generalized. Mucin deposition in the pretibial area is often associated with Graves’ disease or other thyroid disorders, a condition referred to as “pretibial myxedema” [2]. Nevertheless, several cases of pretibial mucinosis in euthyroid patients have been documented. Obesity-associated lymphedematous mucinosis (OALM) is an emerging variant of pretibial mucinosis occurring in obese individuals, characterized by chronic leg lymphedema with mucin deposition in the pretibial dermis [3]. This condition can be distinguished from pretibial myxedema by the absence of thyroid disease and by its clinicopathological features [4]. OALM is rare, and only a few cases have been reported. We report a case of pretibial mucinosis in an obese patient with a history of bilateral leg edema.

Case Presentation

An 85-year-old female presented with bilateral leg edema for 1 year. She denied orthopnea, paroxysmal nocturnal dyspnea, or chest pain. She was obese (BMI 39 kg/m²). She had a history of leiomyoma and had undergone total hysterectomy 4 years earlier. On physical examination, there were ill-defined, brownish to erythematous, indurated plaques and nodules on both lower legs with pitting edema (shown in Fig. 1). Cardiovascular examination and investigations were unremarkable. Thyroid function test results were within normal limits. Color Doppler venous ultrasonography of both lower extremities revealed no evidence of deep vein thrombosis. Lymphoscintigraphy demonstrated patent lymphatic drainage in both lower extremities. An incisional biopsy of the lesion on her left lower leg was performed.

Fig. 1.

Clinical features of OALM. a Bilateral ill-defined erythematous indurated plaques and nodules on both lower legs with edema. b Close-up view of the lesion.

Histopathology showed epidermal acanthosis with increased basal hyperpigmentation. The dermis exhibited mixed inflammatory cell infiltration, an increased number of fibroblasts, and vascular proliferation with lymphangiectasia. Colloidal iron stain demonstrated increased dermal mucin in the upper dermis and perivascular areas (shown in Fig. 2). Perls’ Prussian blue stain was negative for hemosiderophages. Based on the patient’s history of obesity, euthyroid status, and skin histopathology findings compatible with lymphedema and increased dermal mucin, a diagnosis of OALM was established. The patient was referred to a dietitian for weight management and advised to use a compression therapy; however, she was subsequently lost to follow-up.

Fig. 2.

Histopathology of OALM. a Epidermal acanthosis, vascular proliferation in the upper dermis, and lymphangiectasia (H&E, ×100). b Mucin deposition in the upper dermis and perivascular areas (colloidal iron stain, ×100). H&E, hematoxylin and eosin.

Discussion

This case report was prepared in accordance with the CARE guidelines. The completed CARE checklist is provided as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/cde/abvag013).

Pretibial mucinosis is classically associated with thyroid disease, particularly Graves’ disease. However, Somach et al. [5] were the first to report six cases of pretibial mucinosis in euthyroid patients. The association of obesity, lymphedema, and pretibial mucinosis was first reported by Tokuda et al. [2], who described the condition as “chronic obesity lymphoedematous mucinosis”. The term OALM was later established by Rongioletti et al. [6].

Table 1 summarizes the characteristics of previous and current cases of OALM. All patients were obese (BMI ≥30 kg/m²), with the majority classified as severely or morbidly obese (BMI ≥35 kg/m²). Patients presented with asymptomatic skin-colored, erythematous, or yellowish papules and nodules on the shins, accompanied by leg erythema and edema. Indurated, woody plaques were also observed, and vesicles could develop. Interestingly, the feet and ankles were spared in this condition. The condition typically follows a chronic course.

Table 1.

Characteristics of case of OALM

Authors	Cases, n	Age/sex	Comorbidities	BMI, kg/m2	Duration	Clinical features	Treatment	Treatment outcomes
Tokuda et al. [2]​​	3​​	76M	–	35.2	4 years	Brownish plaques and vesicles	–	–
		60F	–	42.5	2 years	Waxy papules	Compressive therapy	Marked improvement
		36M	–	51	6 months	Well-circumscribed, indurated plaques	Topical corticosteroid	N/A
Rongioletti et al. [6]	5	69M	Hyperglycemia, hyperuricemia	>40	4 years	Skin-colored papules and nodules with erythema	Hypocaloric diet	Marked improvement
		64F	Hyperglycemia	43	4 years	Skin-colored papulovesicles	Weight reduction
		47F	–	35	Several years	Yellowish-red papules and nodules	–
		51F	–	43	2 years	Papules	–
		69F	Diabetes	47	3 years	Papules, nodules, and vesicles	Hypocaloric diet
							Weight reduction
Brauns et al. [7]	1	78F	History of endometrial cancer status post-hysterectomy and adnexectomy	32	3 years	Erythematous waxy plaques and nodules	Topical corticosteroids	No improvement
Woolf et al. [8]	1	71M	Diabetes, COPD, epilepsy	40	3 years	Multiple pinkish papules and well-demarcated tan-pink indurated plaque	Weight reduction	Minimal improvement
							Compressive therapy
Karadag et al. [9]	1	71F	–	37.1	1 year	Erythematous plaques and semitranslucent papulonodular lesions	Pentoxifylline	Minimal improvement
							Topical corticosteroid
							Intralesional corticosteroid
							Weight reduction
Ferreli et al. [4]	2	76F	Diabetes, hypertension	N/A	N/A	Translucent erythematous, skin-colored papules and nodules	Low-calorie diet	Marked improvement
							Compressive therapy
		72F	Chronic heart failure, hypercholesterolemia, arterial hypertension, diabetes mellitus type II	38.7	1 year	Erythematous, semitranslucent papules and nodules	No treatment given (loss to follow-up)	N/A
Pai et al. [10]	2	70F	Asthma, hypertension	40	3 years	Tense bullous lesions, erythematous papules and nodules	Weight reduction	N/A
		74F	–	35	2 years	Erythematous nodular plaque	Weight reduction	N/A
Kobkurkul et al. (present report)	1	85F	Leiomyoma, status post-total hysterectomy	39	1 year	Skin-colored to brownish plaques and nodules	Weight reduction	N/A
							Pressure bandage

Overall characteristics of OALM cases reported in the literature.

Pitting edema with sparing of the feet and ankles has been reported in the majority of cases.

All lesions were reported to occur on the legs.

Common histopathologic features included mucin deposition in the upper dermis, dermal edema and fibrosis, angioplasia, vertically oriented blood vessels, and lymphangiectasia.

Histopathology demonstrated mucin deposition in the superficial dermis. Dermal edema, fibrosis, angioplasia, vertically oriented and thickened vessels were also observed. Dilated lymphatic channels were reported in several cases. The histopathology of OALM differs from that of pretibial myxedema, in which mucin deposition extends into the deep reticular dermis and subcutis. Moreover, angioplasia and vascular thickening are uncommon in pretibial myxedema [6, 10]. It has been proposed that the pathogenesis of the disease involves local hypoxia secondary to lymphatic stasis, which promotes fibroblast proliferation and excessive mucin deposition [3, 11]. The underlying mechanism of lymphedema associated with obesity remains unclear, and lymphoscintigraphy findings are often normal [2, 8]. The disease generally follows a benign course. Regarding treatment modalities, weight reduction and compression therapy have been reported as the most effective approaches to ameliorate lymphatic stasis and cutaneous manifestations [2, 4, 6]. Topical and intralesional corticosteroids have been used in some reports, with slight or no improvement [7, 9]. Pentoxifylline was also mentioned in one case report, with no improvement observed [9].

In conclusion, OALM is an emerging and rare variant of pretibial mucinosis. It should be considered in the differential diagnosis of mucinous lesions occurring in obese patients with euthyroid status. Histopathological examination is essential for distinguishing this condition from other causes of cutaneous mucinosis.

Statement of Ethics

Written informed consent was obtained from the patient for publication of this case report and any accompanying images. Ethical approval was not required for this study in accordance with local and national guidelines.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

This study was not supported by any sponsor or funder.

Author Contributions

Pantaree Kobkurkul contributed to case conceptualization and manuscript writing. Penvadee Pattanaprichakul and Panitta Sitthinamsuwan contributed to histopathological evaluation and interpretation. Panwadee Thongjaroensirikul contributed to case conceptualization, supervision, and preparation of the final manuscript draft.

Funding Statement

This study was not supported by any sponsor or funder.

Data Availability Statement

All data relevant to this manuscript are contained in the publication. Further inquiries can be directed to the corresponding author.