Obesity-Associated Lymphedematous Mucinosis: Two Further Cases and Review of the Literature

Abstract

Cutaneous mucinoses are a group of conditions characterized by increased amounts of acid mucin in the dermis. They can be generalized or localized and occur isolated or in the setting of systemic diseases. Obesity-associated lymphedematous mucinosis is a distinct variant of mucinosis occurring in obese patients without any thyroid dysfunction. So far, only few cases of this rare condition have been reported in the English literature. Here, we describe two new cases and discuss some histological differences with the pretibial myxedema.

Introduction

Obesity-associated lymphedematous mucinosis (OALM) is a rare and newly recognized disorder that can clinically mimic pretibial myxedema [1, 2]. The absence of thyroid disease and histological findings can differentiate the two conditions [1].

Report of Cases

A 76-year-old obese, diabetic woman with a long history of hypertension came to our department for the presence of slowly growing asymptomatic papular lesions on both legs. She had a history of prolonged swelling of the lower extremities and referred the lesions firstly had appeared over her right leg and subsequently involved the left leg. On dermatological examination, skin-colored to red, densely grouped, papulo-nodular lesions were present on both legs, affecting mainly the pretibial region. Some of them were translucent with a yellowish hue, others light brownish in color and bigger in size, with crust covering superficial erosion. A pitting edema was present on both legs (Fig. 1). No signs of venous insufficiency were present.

Fig. 1.

Patient 1: translucent erythematous, skin-colored papulo-nodular lesions on the shins of edematous legs.

The second patient was a 72-year-old woman presenting with swelling and erythema on both her legs for 1 year. She had been overweight for 20 years (height 159 cm, weight 98 kg, and body mass index 38.7 [class II obesity]). On physical examination, reddish, semi-translucent papulo-nodules on both edematous legs were present (Fig. 2). Moreover, the patient had chronic heart failure, hypercholesterolemia, arterial hypertension, and type II diabetes mellitus. Venous duplex ultrasonography did not reveal an evident venous insufficiency. No therapy was given and she was lost to follow-up.

Fig. 2.

Patient 2: semi-translucent, papulo-nodular lesion on an edematous, reddish background.

A skin biopsy, taken form a papular lesion on the leg of both patients, gave the same histopathological results, i.e., epidermal atrophy, dermal edema, angioplasia with thick-walled vertically running dermal vessels embedded in a fibromyxoid matrix. Prominent stellate fibroblasts and a discrete perivascular lymphocytic infiltrate were present. The Alcian Blue pH 2.5 histochemical staining confirmed the presence of mucin in the superficial dermis (Fig. 3, Fig. 4).

Fig. 3.

H&E. Epidermal atrophy, mucinous edema of the upper part of dermis with increased stellate fibroblasts (inset).

Fig. 4.

H&E (inset: Alcian Blue pH 2.5). Angioplasia with vertically running thickened capillary vessels. Moderate amount of mucin in the dermis (inset).

Pretibial mucin deposition is a phenomenon that occurs in association with thyroid diseases (pretibial myxedema) or without any thyroid dysfunction (pretibial mucinosis) [1]. OALM represent a type of pretibial mucinosis, strongly associated with obesity, characterized by skin-colored to erythematous-yellowish semi-translucent papules, plaques and nodules, arising in an edematous lymphostatic skin of the lower legs, especially on the shins [1].

The pathogenesis of this rare condition has not been fully elucidated and, to the best of our knowledge, 22 cases have been reported in the English literature and are summarized in Table 1[1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11]. Lymphatic stasis, stimulated by the obesity, seems to determine a local hypoxia leading to the accumulation of mucin [4]. This appears to be induced by the deposition in the interstice of plasmatic proteins due to a defect of the lymphatic drainage and the ischemia favored by a frequently associated venous insufficiency. A distinct histopathological picture for OALM, different from classic pretibial myxedema and from venous insufficiency-associated dermal mucinosis, has been defined whose histopathological clues are (1) epidermal atrophy, (2) moderate amount of dermal mucin in the superficial dermis, (3) angioplasia made by vertically running vessels in the superficial and mid dermis, (4) increased stellate or linear fibroblasts; subepidermal blister can be occasionally seen [2]. On the contrary, pretibial myxedema shows an acanthotic epidermis with ortohyperkeratosis and diffuse striking mucin deposition throughout all the reticular dermis without evident angioplasia. Dermal mucinosis in the setting of chronic venous insufficiency is characterized by abundant dermal mucin deposition, a slight increase in small blood vessel density, slightly thickened vessel walls, and no inflammatory infiltrate.

Table 1.

Literature review of all cases of cutaneous pretibial mucinosis

Patients	Age, years/sex	Diagnosis	Comorbidities	Follow-up	References
6	38/M	Elephantiasis verrucosa nostra	Obesity	None	Somach et al. (1993) [1]
	77/M	Stasis dermatitis
	66/M	Not specified
	49/M	Pretibial myxedema
	70/M	Pretibial myxedema
	80/M	Elephantiasis verrucosa nostra
1	44/F	Pretibial mucinosis	Venous	None	Kim et al. (2002) [10]
			insufficiency
3	76/M	OALM	Obesity	1. Pressure bandage therapy	Tokuda et al. (2006) [3]
	60/F			2. Pressure bandage therapy effective only for the papules
	36/M
				3. Woody plaque with corticosteroids
5	69/M	OALM	Obesity	1&5 hypocaloric diet (1,200 cal/day)	Rongioletti et al. (2009) [2]
	64/F
	47/F			2&5 weight loss with clinical improvement
	51/F
	69/F
2	73/M	Dermal mucinosis	Venous	Triamcinolone laser, topical steroids, no improvement	Pugashetti et al. (2010) [9]
	61/M		insufficiency
1	46/M	Pretibial mucinosis	None	Triamcinolone acetonide ointment under occlusion, moderate improvement of pruritus and slight improvement in appearance	Mir et al. (2011) [8]
1	71/M	OALM	Obesity	Compression hosiery, weight loss, minimal improvement	Woolf et al. (2014) [7]
1	78/F	OALM	Obesity	Suggested weight loss	Brauns et al. (2013) [5]
1	70/F	Pretibial mucinosis	Obesity	None	Milman et al. (2016) [4]
1	71/F	OALM	Obesity	Pentoxyphyllin 400 mg, clobetasol 17-propionate 0.05% cream, triamcinolone acetonide injections, weight loss suggested	Karadag et al. (2014) [6]
1	72/F	Pretibial mucinosis	Venous	CO2 laser vaporization, improvement	Castiñeiras et al. (2009) [11]
			insufficiency
2	72/F	OALM	Obesity	Low-calorie diet, pressure improvement	Present paper
	76/F

OALM, obesity-associated lymphedematous mucinosis.

OALM has usually a benign course but can cause a cosmetic disfigurement. Although there is no commonly accepted treatment, pressure bandage and diet restriction has been described as helpful. In our first case, gradual compression in association with a low-calorie diet obtained an improvement of the edematous stasis and the dermatologic condition.

Statement of Ethics

The study protocol has been approved by the local ethics committee and the subjects have given their informed consent to participate.

Disclosure Statement

The authors have no conflict of interest to declare.