A case of scleromyxedema responding to lenalidomide and dexamethasone.

Sir,

Scleromyxedema is a rare and distinctive variant of cutaneous mucinosis with unknown etiopathogenesis. A 46-year-old male patient presented to the dermatology department with a 1-year history of raised skin lesions associated with skin thickening and slight itching. The eruption, initially located on the face and neck, had recently spread to the hands, forearms and upper trunk. Examination of face revealed diffuse erythema, induration, coarsening, and grooving both in the forehead lines and in the lateral portions of the chin. diffuse flesh colored waxy firm papules were seen on the neck, [Figure 1a], lower and [Figure 1b] upper extermities chest and wrist and ears. The [Figure 1c] coarsening of skin folds and diffuse erythema were apparent on the back. General physical examination was normal. Systemic examination was normal. The clinical presentation was suggestive of scleromyxedema. Skin biopsy revealed sparse superficial and deep perivascular lymphocytic infiltrate with abundant mucin and an increased number of fibrocytes within the reticular dermis. Special stains for mucin revealed bluish stained mucinous material [Figures 2 and 3].

Figure 1

(a) Flesh coloured waxy papules onthe neck, (b) upper extremeties, chest and wrist, (c) coarsening of skin fold

Figure 2

Histopathological examination revealed a sparse superficial and deep perivascular lymphocytic infiltrate with abundant mucin within the reticular dermis (H and E, ×10)

Figure 3

Histopathology in higher magnification shows mucin within the reticular dermis and showed an increased number of fibrocytes (H and E, ×40)

Complete blood count revealed hemoglobin 13.4 gm/dl and total leukocyte count 7000/cu.mm. Platelet count was 2.19 lacs/cu.mm. Fasting and post prandial blood sugar levels were 80 mg/dl and 130 mg/dl, respectively. His liver functions tests SGOT/SGPT were 30/32 U/l, blood urea nitrogen was 15 mg/dl, and serum creatinine was 1.1 mg/dl. Antinuclear antibody and thyroid markers were normal. Enzyme-linked immunosorbent assay for human immunodeficiency virus was negative. Bone marrow examination showed less than 5% plasma cells. Serum protein electrophoresis showed M band 15.5 gm/litre (gamma light chain).

Radiological investigations revealed a normal chest radiograph. Whole body bone scan was normal. The patient was diagnosed as a case of monoclonal gammopathy of undetermined significance.

Our patient was referred to an oncologist for further treatment. He was treated with oral lenalidomide 10 mg and aspirin 150 mg daily along with dexamethasone 4 mg in divided doses once a week, which was continued for 3 months. There was substantial improvement with this treatment. His complete blood count was normal after treatment, M Band reduced to 2.0 g/litre post treatment. At follow-up after 3 months of chemotherapy, papular skin lesions and induration on the face [Figure 4a] and chest [Figure 4b] had resolved [Figure 4].

Figure 4

Post chemotherapy papular lesion and indurated lesions on face (a) and chest (b) had resolved after 3 months of treatment

Scleromyxedema is a generalized and sclerodermoid form of lichen myxedematosus. It usually affects middle-aged people, with equal incidence in women and men. Diagnostic criteria are as follows:[1]

Generalized papular and sclerodermoid eruption,

The presence of mucin deposition, fibroblast proliferation and fibrosis histopathologically,

Paraproteinemia, i.e., monoclonal gammopathy (typically IgG λ), and

Absence of thyroid dysfunction.

The present therapeutic approach for scleromyxedema is based on its supposed link with monoclonal gammopathy. Therefore, practitioners use treatments that target the plasma cell dyscrasia such as melphalan and, more recently, thalidomide with good but often transitory results on the skin. Lenalidomide is an oral immunosuppressive agent. It shows good response in myeloma patients. This drug is a thalidomide analogue with better tolerability profile and reduced incidence of side-effects such as somnolence, constipation, and neuropathy, thus allowing long-term administration. Lenalidomide has immunomodulatory properties due to the stimulation of NK-cell activity and the increased IL-2 production, which enhances T-cell activity. These properties make lenalidomide a good maintenance treatment even though side effects, such as cytopenia and thromboembolic events, have been reported.

Induction therapy with lenalidomide and dexamethasone to reduce the tumor burden, followed by maintenance therapy with low-dose lenalidomide is an effective treatment approach, as found in a previous study.[2] Low-dose glucocorticoid at the time of biologic progression, which appeared to provide disease control in some patients.

Early treatment with lenalidomide and dexamethasone, followed by maintenance therapy with lenalidomide, in patients with high-risk smoldering multiple myeloma significantly delayed the time to progression to symptomatic disease and resulted in an overall survival benefit. The orally administered treatment regimen was associated with an acceptable toxicity profile.[2] Lenalidomide could also be an alternative to thalidomide for patients showing neuropathy, frequently associated with scleromyxedema.[3] Thalidomide (or lenalidomide) and/or systemic steroids are considered the second line of treatment, more often in combination with intravenous immunoglobulins than as monotherapy in the treatment of scleromyxedema.[4] Dexamethasone therapy seems to target both the paraprotein production and the hyperactive fibroblast through its immunosuppressive and antifibroblast effects.[5]

We decided to use a lower dose of lenalidomide of 10 mg as the author had noticed that higher doses of 25 mg are not tolerated by most of the myeloma patients and neutropenia is more common with higher doses. We noted a good response with 10 mg of lenalidomide because most of the skin lesions resolved in 5–6 weeks of starting the pulse dexamethasone and low dose lenalidomide. This case also highlights the lack of relationship between the skin healing and the evolution of the gammopathy, as already described in the literature. To date, the factor inducing skin fibrosis remains unknown.[3]

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Conflicts of interest

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