Case report
Scleromyxoedema in a 70-year-old woman – case report and review of the literature

Introduction

Lichen myxoedematosus (LM) is a chronic and progressive disease, clinically characterized by lichenoid papules, nodules and/or plaques caused by mucin deposition, with concomitant fibrosis, without thyroid disease [1].

For many years no uniform classification taking into account different variants of the disease existed. The classification proposed by Rangioletti in 2007 distinguishes 3 main forms of lichen myxoedematosus: (1) scleromyxoedema (SM) with monoclonal gammopathy, (2) limited form and (3) atypical variants: SM without gammopathy, limited form with monoclonal gammopathy and/or with visceral involvement [2].

Lichen myxoedematosus occurs mainly in middle aged adults, with equal frequency in males and females. In some cases it may be an important clinical problem because of therapeutic difficulties, possible monoclonal gammopathy development and visceral involvement which may lead to death [3, 4]. The relationship between scleromyxoedema and gammopathy was first described in 1963 [2].

To confirm the diagnosis of SM a patient needs to fulfil the following criteria: (1) generalized papular eruption, (2) mucin deposits, proliferation of fibroblasts and fibrosis in histopathological examination, (3) monoclonal gammopathy and (4) lack of functional disorder of the thyroid gland. [1] The disease is an irreversible process, although there are a few case reports of its spontaneous regression [2].

Numerous, 2-3 mm in diameter, hard, waxy papules on the surface of the hands, forearms, head, neck, chest and thighs are typical findings in patients with SM. The surrounding skin seems to be shiny and infiltrated. Patients often complain of itching.

Visceral involvement is often seen in patients with SM. The most frequent systemic symptom is monoclonal gammopathy, which is observed in 83.2% of all patients [3]. It should be noted that paraproteinaemia may be the cause of the secondary haematological disorders, especially multiple myeloma (10% of all patients). Other possible organ complications in the course of SM are presented in table 1.

The association between monoclonal gammopathy and scleromyxoedema is still being discussed. However, it seems that the titre of paraproteins does not correlate with severity of the disease [2]. It is believed that paraproteins are responsible for fibroblasts’ proliferation as well as for mucin deposition in the skin. Some other factors, which circulate in the serum, are also suspected. They may stimulate fibrosis by the synthesis of hyaluronic acid, which is probably mediated by prostaglandins [5].

The histopathological picture is also typical for SM. A triad of symptoms is seen: mucin deposits (reticulate layer of the dermis), deposits of collagen, and irregular dispersed fibroblasts. The epidermis may be unchanged or thin as a result of accumulating underneath deposits and fibrosis.

The treatment of scleromyxoedema is extremely difficult and its outcome is often disappointing. In consequence there are many controversies about effective therapy.

We present a case of a 70-year-old patient with scleromyxoedema.

Case report

The disease began 5 years ago. The patient complained of facial skin thickening accompanied by increased stiffness and tension around the mouth, joint pain and sclerodactyly (fig. 1-3). Based on the clinical and histopathological picture (skin biopsy) the diagnosis was scleroderma. To exclude visceral involvement in the course of the disease radiological examinations were performed (chest X-ray, ultrasound of abdomen). Lung function was also normal. The titre of antinuclear antibodies (ANA-Hep2) in the serum was negative. Finally, based on the results of diagnostic procedures, acroscleroderma was diagnosed. The patient was treated with prednisolone, Piascledine and pentoxifylline for a few months without satisfactory results.

After a while the patient noticed small papules on her face, distal parts of limbs and sacral area, accompanied by intense itching. The clinical picture suggested mucinosis. Therefore a skin biopsy was taken again, in order to verify the diagnosis. The histopathological examination revealed mucin deposition in the involved skin. Monoclonality of gamma globulins was also confirmed in plasma protein electrophoresis. The clinical picture and the results of performed laboratory tests suggested the diagnosis of scleromyxoedema. Cyclophosphamide (50 mg p.o. a day) and prednisone (40 mg a day) were administered but also without result. Finally melphalan, as a first line treatment in SM, was used. Partial regression was observed but it was temporary. Due to the significant progression of the disease, cyclophosphamide intravenously (1000 mg) every 6 weeks was administered with good results. The patient has undergone 5 cycles of the therapy.

Discussion

Treatment of scleromyxoedema is an important problem for practitioners. Effective therapy of this disease is unknown. This is due to the rarity of SM and the lack of results of controlled clinical trials evaluating the effectiveness of selected therapeutic approaches.

Desai and James [12] proposed melphalan, glucocorticosteroids and plasmapheresis as the first line treatment in SM. But in some cases therapy with isotretinoin or acitretin should also be taken into consideration. However, it seems that all of these methods act only symptomatically. They have no influence on the pathogenesis of the disease. It is recommended to use 2CDA, cyclophosphamide, cyclosporine, methotrexate, thalidomide, extracorporeal photopheresis, autologous bone marrow transplantation, immunoglobulins intravenously or photo- ­­chemotherapy (PUVA therapy) in patients who are resistant to the therapy proposed above [12].

Based on the clinical observations it is believed that melphalan can be an effective therapeutic option. However, its use may be limited by its toxicity (myelotoxicity). That is why patients who are treated with low doses of melphalan require regular monitoring of blood counts [13]. Long-term therapy with melphalan is also a risk factor for life-threatening septic complications as well as the development of haematological malignancies [3, 13].

The effects of glucocorticoids in the treatment of SM are limited, although there are reports showing the effectiveness of high doses of dexamethasone [14].

It is believed that the use of immunoglobulins intravenously can also be effective in SM, although it may be associated with serious side effects [15-17].

Autologous bone marrow transplantation is speculated to be an effective method in the treatment of SM (alone or in combination with melphalan [18, 19] or thalidomide [20]).

Based on the current state of knowledge, it seems that the selection of the therapeutic method in SM should be an individual matter. Aggressive therapeutic approaches should be reserved only for patients with a very severe course of the disease.

References

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