Stasis Mucinosis: Insights Into Euthyroid Localized Mucinosis

Cutaneous mucinosis are characterized by an abnormal accumulation of mucin within the skin.¹ Few articles have been published describing stasis mucinosis as an etiology. Stasis mucinosis and obesity-associated lymphedematous mucinosis (OALM) have been described as 2 diagnostic entities; however, the authors believe they represent the spectrum of euthyroid mucin depositional disease in varying clinical settings. 

The case of a morbidly obese African American man in his late 60s with stasis mucinosis in the context of normal thyroid function tests is presented.

A morbidly obese (body mass index: 37.7 kg/m²) African American man in his late 60s presented to the emergency department of the University of Miami Hospital (Miami, FL) with a 3-month history of bilateral swelling of legs and feet. The patient complained of recent increased pain from an open wound in his left hallux that developed as a result of bumping his left foot in the kitchen a few days prior to presentation. His primary care physician was treating him with compression therapy. His medical history included hypertension, hyperlipidemia, and cerebral palsy. His home medications included aspirin, metoprolol, and paroxetine.

On skin examination of the lower extremities, he had severe (3+) edema, varicosities and diffuse induration with red scaly plaques, and multiple raised areas of verruciform papules, nodules, and varicosities (Figure 1A, 1B). The left hallux had an ulcer measuring 0.5 cm x 0.5 cm without drainage or fluctuance (Figure 1C) with an overlying flap of skin adherent but not covering the entire wound. In addition, his feet and toes had scaly patches.

Laboratory evaluation had leukocytosis (12.8 x 10³/uL) with a predominance of neutrophils (80.7%), anemia (hemoglobin 12.0 g/dL), increased creatinine levels (1.21 mg/dL), hypocalcemia (8.4 mg/dL), hypoproteinemia (5.4 g/dL), increased erythrocyte sedimentation rate (44 mm/hour), and C-reactive protein (16.4 mg/dL); thyroid function tests were normal. Radiographs of his left foot and arterial and venous Doppler scans of both legs found patent arteries and no venous thrombosis. Venous reflux was difficult to assess due to the patient’s body habitus and bilateral edema.

He was admitted with the diagnosis of lymphedema and cellulitis, received intravenous piperacillin/tazobactam (4.5 g every 8 hours) and vancomycin (750 mg every 12 hours), and was discharged with oral doxycycline.

A skin biopsy taken from the left lower leg found advanced stasis changes, including the proliferation of grouped small blood vessels in the papillary dermis, dermal fibrosis, and abundant hemosiderin depositions. The colloidal iron stain highlighted increased mucin deposit mainly in the upper dermis and minimally in the deep dermis (Figure 2). Pathologic diagnosis of stasis mucinosis was rendered.

Cutaneous mucinosis are characterized by an abnormal accumulation of mucin within the skin.¹ They are classified into: (1) primary mucinosis and (2) secondary mucinosis, in which the mucin deposition is associated with a secondary disorder (Figure 3). Cutaneous mucinosis can further be classified into localized and generalized.¹

The pathophysiology responsible for dermal mucin deposition in the setting of venous insufficiency is imprecise, but hypoxia may play a principal role. Fibrinogen leakage into surrounding tissues causes edema, therefore decreasing local oxygen delivery.² Chondrocytes and fibroblasts, in response to reduced oxygen tension, increase the production of hyaluronic acid.^2,3 The extracellular matrix provides a supportive scaffold for vascular endothelium and angiogenesis.^2,4 

In addition, the role of lymphedema must be considered as another possible hypothesis or cofactor of this entity. Venous insufficiency can lead to increased hydrostatic pressure and increased lymphatic load.² In lymphedema, the abnormal accumulation and stasis of protein-rich lymphatic fluid leads to accumulation of lymphatic and interstitial fluid within the dermis. The extravascular accumulation of plasma proteins can stimulate fibroblasts to further synthesize and deposit glycosaminoglycans.^2,5

Few articles have been published describing stasis mucinosis as an etiology. Pugashetti et al² reported 2 cases of localized cutaneous mucinosis secondary to venous insufficiency, in the absence of thyroid dysfunction, lupus erythematosus, dermatomyositis, scleroderma, granuloma annulare, graft versus host disease, mucin deposition postultraviolet, or photochemotherapy treatment.² The clinical presentation was characterized by painful plaques in the context of edematous bilateral lower extremities.² 

This condition was first described by Somach et al in 1993⁶ when a comparison of skin biopsies of patients with Graves’ disease versus patients with pretibial myxedema with no thyroid disease was done.^6,7 Among the patients with pretibial myxedema with no thyroid disease, 10 had stasis dermatitis. Important histological differences between these 2 entities were appreciated. In the skin biopsies of the patients with Graves’ disease, there was normal-appearing collagen in the superficial papillary dermis, mucin deposition in the reticular dermis, lack of mucin deposition in the superficial papillary dermis, and angioplasia. These features mostly were absent in the context of stasis dermatitis. Moreover, hemosiderin and mucin deposition in the papillary dermis was found in the majority of the specimens from the patients with stasis dermatitis.⁷

In the differential diagnosis, pretibial myxedema, also called thyroid dermopathy, should always be considered. Pretibial myxedema forms part of the classical triad of Graves’ disease (goiter, ophthalmopathy, pretibial myxedema).⁸ Pretibial myxedema is accompanied by abnormal thyroid function test. It may spread to the ankle and dorsum of the foot and present on the elbows, knees, upper back, and neck.⁸ Also, the clinical changes observed in pretibial myxedema may masquerade as venous leg ulcers.⁹

Chronic obesity lymphedematous mucinosis or OALM is a newer etiology that is characterized by pretibial mucinosis in the absence of thyroid disease and occurs in morbidly obese patients.¹⁰ It presents with bilateral lower extremity pitting edema of gradual and painless onset. Biopsy shows small vessels with hemosiderin deposition and mucin deposition at the superficial papillary dermis and around the vessels.¹⁰

Rongioletti et al¹¹ described 5 patients with OALM; all patients were middle aged or elderly and morbidly obese. The patients had bilateral lower extremity pitting edema sparing the feet, semitranslucent papules and/or nodules, and sometimes vesicles also were appreciated. On histology, mucin deposition stained positively with alcian blue and colloidal iron. Interestingly, when the patients lost weight, there was an improvement on the skin manifestations.¹¹ A 78-year-old woman¹² and a 71-year-old woman¹³ were reported with the same etiology. The most recent publication described 2 patients with OALM.¹⁴

Stasis mucinosis and OALM have been described as 2 diagnostic entities; however, the authors believe it may be the same etiology caused by shared pathophysiological mechanisms. Dermal mucinosis needs extensive evaluation, including thyroid diseases. It is also important to remember that it can occur in the setting of obesity, lymphedema, and/or venous insufficiency.

Authors: Penelope A. Hirt, MD¹; Flor E. MacQuhae, MD¹; Jeong Hee Cho-Vega, MD, PhD²; and Robert S. Kirsner, MD, PhD¹

Affiliations: ¹Department of Dermatology, Miller School of Medicine, University of Miami, Miami, FL; and ²Department of Pathology, Dermatopathology, Sylvester Comprehensive Cancer Center and Miller School of Medicine, University of Miami

Correspondence: Robert S. Kirsner, MD, PhD, Department of Dermatology and Cutaneous Surgery, University of Miami, Miller School of Medicine, 1600 NW 10th Avenue, Miami, FL 33136;
rkirsner@med.miami.edu 

Disclosure: The authors disclose no financial or other conflicts of interest.