The terms lichen myxedematosus, papular mucinosis, and scleromyxedema are used interchangeably to describe the same disorder. A spectrum of disease appears to exist, with the more localized, less severe forms, which are generally called lichen myxedematosus or papular mucinosis, and the more sclerotic, diffuse form, which is referred to as scleromyxedema. Lichen myxedematosus is a rare skin disorder characterized by fibroblast proliferation and mucin deposition in the dermis, in the absence of thyroid disease. Sclerotic features, systemic involvement, and monoclonal gammopathy are absent in localized lichen myxedematosus.
The etiology is unknown; however, the disease is commonly associated with plasma cell dyscrasia. The basic defect is hypothesized to be a fibroblast disorder, which causes the increased mucin deposition in the skin. The cytokines interleukin (IL)–1, tumor necrosis factor (TNF)–alpha, and TNF-beta may play a role. Most patients have a monoclonal paraprotein band, usually of the immunoglobulin G (IgG) type. The association between this paraprotein and the mucin deposition is not clear, and the protein does not directly stimulate fibroblast proliferation. Paraprotein levels have not been shown to correlate with disease severity, response to therapy, or disease progression.
For lichen myxedematosus, the prognosis is a chronic course with little tendency for spontaneous resolution. Although most patients have a monoclonal paraproteinemia, they rarely have associated multiple myeloma. However, when myeloma is present, the patient generally has a poor prognosis.
Scleromyxedema usually has a poorer prognosis than that of the other forms. Typical causes of death include complications of systemic therapeutic agents such as melphalan or systemic disease such as cardiovascular involvement.
Patients with cardiac or pulmonary involvement also have a poor prognosis.
Patients with lichen myxedematosus have a long-term, disfiguring, possibly disabling disorder. The risks and benefits of systemic therapy must be weighed carefully.
Patients report a slow onset of asymptomatic or mildly pruritic papules, which may be localized or generalized. Patients are otherwise healthy and do not have systemic symptoms.
Scleromyxedema
Patients with this form present with more widespread progressive induration and decreased mobility of the face, fingers, and extremities. Patients are also noted to have cysts and urticarial lesions. Patients may report systemic symptoms, such as dysphagia or weakness, and symptoms that resemble those of organic brain disease.[1, 2]
Montgomery and Underwood described four clinical presentations and grouped the different manifestations in a classification system as follows[3] :
Generalized lichenoid papular form
Discrete papular form
Localized or generalized lichenoid papules
Urticarial plaques and nodular eruptions that usually lead to the lichenoid form
The primary lesion is a 2- to 4-mm, dome-shaped, and flesh-colored or erythematous papule. Regarding the distribution, these lesions may coalesce into grouped lichenoid papules and are found on the dorsal hands, face, or extensor surfaces of the arms and legs. Papules often have a striking pattern of parallel ridges. In patients with the generalized lichenoid form, facial ridges and facial folds may be distorted; this condition is called leonine faces. Patients with leonine faces may have difficulty opening their mouths.
Note the image below.
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Grouped, erythematous, flesh-colored, dome-shaped papules are present on the hand and fingers.
Scleromyxedema
The primary lesions may involve widespread erythematous, indurated skin that resembling scleroderma, with diffuse tightness of the skin. The range of motion of the face, fingers, and extremities is decreased. The systemic manifestations include restrictive and obstructive pulmonary dysfunction, cardiovascular abnormalities, and polyarthritis. Obstructive and restrictive lung disease is often manifested by dyspnea on exertion.
Gastrointestinal symptoms (most commonly dysphagia) are related to esophageal aperistalsis. Severe proximal muscle weakness, polyarthritis, and symptoms resembling those of organic brain disease are present. Inflammatory myopathy is also reported. Ophthalmologic symptoms include ectropion and corneal opacities. Cardiovascular abnormalities occur in 10% of cases. One study revealed that digital vasoreactivity is the most common vascular abnormality.
Lesions have large depositions of mucin in the dermis. Numerous plump stellate fibroblasts develop throughout the dermis. There is increased collagen deposition. The mucin stains with periodic acid-Schiff and Alcian blue at pH 2.5 but not pH 0.4, and it metachromatically stains with toluidine blue at pH 3.0. The mucin has been identified as hyaluronic acid, a nonsulfated acid mucopolysaccharide.[4]
Note the images below.
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Low-power photomicrograph of a histopathologic specimen demonstrates the wide separation of the collagen fibers near the large collection of mucin in ....
View Image
High-power photomicrograph of a histopathologic specimen reveals the large collections of mucin and plump stellate fibroblasts in the dermis.
The treatment of lichen myxedematosus is difficult and often ineffective. Many therapeutic approaches have been tried.
Melphalan used to be the main treatment for scleromyxedema; however, it may have contributed to patients deaths from inducement of hematologic malignancies.[5]
These approaches include treatment with retinoids, orthovoltage radiation,[6] electron beams, high-dose dexamethasone, psoralen UV-A (PUVA), plasmapheresis, extracorporeal photophoresis, dermabrasion, and carbon dioxide laser excision.[7] Therapeutic improvements have been reported with the use of intravenous immunoglobulins with or without thalidomide or, more recently, lenalidomide, an analogue of thalidomide.[5, 8, 9] Successful treatment is reported with melphalan, dexamethasone, and thalidomide maintenance therapy.[10]
High-dose melphalan followed by autologous stem cell transplantation was reported as effective.[11]
Topical tacrolimus reportedly has been successful in treating localized disease in a few patients.[12]
Various reports in the literature describe treatment successes and failures with these methods.
A 2004 article reported improvement with thalidomide in 3 patients in whom other therapies had failed. All 3 showed marked improvement of skin lesions within the first 2 months of therapy and continued improvement after 4 months of therapy. The doses of thalidomide ranged from 100 mg at bedtime to 400 mg in divided doses; the adverse effects were better tolerated at the 200-mg/d dose in divided doses.[13] Adverse effects of thalidomide most commonly include mild sedation and constipation. Thalidomide is also teratogenic.
Finally, nerve conductions studies have revealed the occurrence of peripheral neuropathy in approximately 25% of patients. In a different 2004 study, high-dose dexamethasone was helpful in 1 patient, who received the drug for 3 weeks, after which it was tapered to a lower dose for 4 months.[14]
A case report using lenalidomide and intravenous immunoglobulins showed significant improvement with persistent remission and no recurrence after 24 months. The lenalidomide has fewer adverse effects than thalidomide, with less neuropathy, somnolence, and constipation.[9]
Intravenous immunoglobulin therapy for scleromyxedema is well documented, although the mechanism of action is not clear. It has been used alone, with thalidomide, or with lenalidomide.[5, 9]
Another consideration, as demonstrated by a case report, was resolution of an atypical case of lichen myxedematosus following treatment for a concomitant infection of hepatitis C with sofosbuvir-velpatasvir therapy.[15]
Successful short-term improvements are reported with melphalan treatment; however, in one study, a significant number of cases had fatal complications due to hematologic malignancies and sepsis.
Clinical Context:
Prednisone is for use in a cyclic protocol with melphalan. It is an immunosuppressant for the treatment of autoimmune disorders; it may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Prednisone stabilizes lysosomal membranes and suppresses lymphocytes and antibody production.
A case report describes systemic corticosteroid therapy; improvement in the skin was noted within 4 weeks.
These agents have anti-inflammatory properties and cause profound and varied metabolic effects. They modify the body's immune response to diverse stimuli.
Clinical Context:
This is off-label use. Intravenous immune globulin is pooled human immune globulins from donors and is used as replacement therapy for primary and secondary immunodeficiencies; it may interfere with Fc receptors on the cells of the reticuloendothelial system for autoimmune disorders, including cytopenias and ITP; it may offer passive immunity by increasing antibody titers and antigen-antibody reaction potential.
Therapeutic improvements have been reported with the use of intravenous immunoglobulins with or without thalidomide or lenalidomide. The dosage is based on case reports and multicenter studies, typically 2 g/kg/month IV divided over 2-5 days, with cycles repeated every 6-8 weeks depending on response and remission. There have been no randomized trials performed.
Clinical Context:
This is off-label use. Its mechanism of action is not fully understood. The active metabolite inhibits pyrimidine nucleotide synthesis and elicits antiproliferative action against T-cells.
Clinical Context:
This is off-label use. Thalidomide suppresses tumor necrosis factor-alpha and down-modulates cell surface adhesion molecules involved in leukocyte migration. Anticancer activity may be due to inhibition of angiogenesis.
Therapeutic improvements have been reported with the use of intravenous immunoglobulin with or without thalidomide or lenalidomide. A case report of marked improvement within 2 months has been described in 3 patients prescribed thalidomide 100 mg PO qd/bid (up to 300 mg/day if needed). Improvement continued after 4 months. GI upset associated with thalidomide may be reduced with divided doses. Another case report describes use of lenalidomide 25 mg/day PO for 3 weeks each month.
Elizabeth A Liotta, MD, Chief Dermatologist and Sole Proprietor, Integrated Skin Care Centers
Disclosure: Nothing to disclose.
Specialty Editors
David F Butler, MD, Former Section Chief of Dermatology, Central Texas Veterans Healthcare System; Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic
Disclosure: Nothing to disclose.
Edward F Chan, MD, Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania School of Medicine
Disclosure: Nothing to disclose.
Chief Editor
Dirk M Elston, MD, Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine
Disclosure: Nothing to disclose.
Additional Contributors
Mark W Cobb, MD, Consulting Staff, WNC Dermatological Associates
Grouped, erythematous, flesh-colored, dome-shaped papules are present on the hand and fingers.
Low-power photomicrograph of a histopathologic specimen demonstrates the wide separation of the collagen fibers near the large collection of mucin in the dermis.
High-power photomicrograph of a histopathologic specimen reveals the large collections of mucin and plump stellate fibroblasts in the dermis.
Grouped, erythematous, flesh-colored, dome-shaped papules are present on the hand and fingers.
Low-power photomicrograph of a histopathologic specimen demonstrates the wide separation of the collagen fibers near the large collection of mucin in the dermis.
High-power photomicrograph of a histopathologic specimen reveals the large collections of mucin and plump stellate fibroblasts in the dermis.
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