On-line version ISSN 1806-4841
An. Bras. Dermatol. vol.79 no.5 Rio de Janeiro Sept./Oct. 2004
Scleromyxedema with associated cardiomyopathy*
Gladys Aires MartinsI; Wadad Gonzaga AbdalaII; Daniela Velozo de AndradeII
IDermatologist, Master's Degree in
IIM.D. in residence
We report a case of scleromyxedema with skin lesions in association with myopathy, esophageal dysfunction and paraproteinemia. During the disease course, the patient developed symptoms of cardiac failure related to a cardiomyopathy, a condition that has been described in up to 10% of patients with scleromyxedema. The clinical, etiologic and therapeutic aspects are discussed in this paper.
Key words: heart failure, congestive; myositis; mucinoses; paraproteinemias.
Scleromyxedema, also known as papular mucinosis and generalized lichen myxedematosus, is a rare disease. Its etiology is not known. It is considered a type of primary cutaneous mucinosis and is associated with high rates of morbidity and mortality.1 It affects adults between the ages of 30 and 70 years, regardless of sex. It is characterized by papulo-lichenoid and infiltrative skin lesions, with firm induration of underlying tissue. The latter might lead to reduced finger mobility and microstomia with subsequent difficulty in opening the mouth.2 Although the disease primarily affects the skin, monoclonal-type paraproteinemia is often detected, which is the paraproteinemia most often found in IgG/A. A few cases of multiple myeloma, leukemia and lymphomas have been reported. Other extracutaneous manifestations include proximal myopathy, inflammatory polyarthritis, laryngeal alterations, esophageal dysfunction, neurological alterations, pulmonary restrictive disease and, less frequently, cardiac alterations. We describe a case with extensive cutaneous lesions in association with esophageal dysfunction, myopathy and monoclonal paraproteinemia, whose disease course was characterized by cardiac alterations.
A 45-year-old melanoderm patient from Freira de Sentana, Bahia state, is a resident of Brasilia, Federal District. The patient first received medical care six years ago and has been undergoing follow up treatment at the ambulatory clinic of the University of Brasilia Hospital Dermatology Service since 1996. Initially, the patient referred to finger paresthesia, hardening of the skin and arthralgia in the proximal interphalangeals of the hands and right knee, in addition to Raynaud's phenomenon. Later, the patient observed hardening of the facial skin around the nose and mouth, as well as of the tongue and lower lip. Four years ago, the patient experienced dysphasia for solids and difficulty in opening the mouth. Two years ago, the patient showed problems in flexing and extending the small joints. There was nothing to report concerning a background of mortality. The physical examination showed diffuse hardening of the skin, giving it a rough aspect with accentuation of skin creases (Figure 1), sclerosis in the fingers (Figure 2), elbows and knees, with reduced joint mobility. Facial involvement was heightened, showing shiny, firm papules in a linear pattern and thick creases on the glabella, the nasal dorsum and chin region (Figures 3 and 4). This led to a reduced labial orifice and incapacitated protrusion of the tongue.
The diagnosis of scleromyxedema was confirmed by a cutaneous biopsy. It showed amorphous basophilic material next to a discrete increase in phagocyte numbers in the upper dermis, and perivascular infiltrate with a presence of mastocytes (Figure 5). The protein immunoelectrophoresis revealed the presence of a monoclonal band with IgG/A, but other laboratory tests, including the tests for presence of rheumatic activity (rheumatoid factor, FAN, anti-DNA, seric complement, anticentromere and Sclero-70 antibodies) were all normal.
The patient was submitted to different systemic treatments: melphalan for a month; methotrexate for nine months; photochemotherapy (PUVA) for six months, and has been using prednisone for two months. The patient referred to improved results with corticotherapy.
Four and a half years into the disease course, the patient started experiencing chest pains that were not related to physical effort. This occurred in association with palpitations and a sensation of weight in the upper left limb, which improved with rest. In December 2001, dyspnea has a sudden onset with medium and low physical effort. The patient also experienced palpitations, MMII edema, and was thereupon hospitalized for assessment. Chest radiography showed increased cardiac layers and prominent lung congestion. Electrocardiogram (ECG) demonstrated LV overload and diffuse changes in repolarization, with a drop in peripheral voltage. The physical examination showed regular cardiac rhythm (RCR) in four beats, systolic breathing in the mitral and tricuspid valves, arterial pressure at 130/80 mm Hg and cardiac frequency at 120 bpm, in addition to respiratory function at 24 imp, hepatomegaly and MMII edema. Left ventricular (LV) function by echocardiogram showed discreet dilatation, involvement of the systolic function, slight mitral, tricuspid and aorta valve insufficiency, LV with diffuse accentuated hypokinesia, except for the posterior wall, and an ejection fraction of 43%. The concluding cardiologic diagnosis was systolic heart failure and dilated cardiomyopathy.
Such a manifestation was considered an extracutaneous manifestation of scleromyxedema. Treatment was started with furosemid, digoxin and enalapril, with oral prednisone reintroduced in a 40 mg daily dose, in addition to motor physiotherapy. The patient progressed with compensation of the CCI, and was discharged following 12 days of hospitalization. A month later, the control echocardiogram showed significant improvement of the LV dilation and discreet improvement of the systolic function, mitral and tricuspid insufficiency, and lung hypertension. The patient is currently undergoing follow up treatment at the HUB Dermatology and Cardiology ambulatory clinic, and is asymptomatic with respect to the cardiovascular device. Improved mobility of the hands and an increase of the oral orifice with the use of prednisone, and motor physiotherapy were reported.
Scleromyxedema is a rare type of papular mucinosis characterized by diffuse sclerosis and generalized lichenoid eruption1. The term was introduced by Gottron in 1954, who considered scleromyxedema a sclerotic variant of papular mucinosis. Since then, several cases have been reported in which lichenoid papules in combination with "scleroderma-like" findings are present.3,4 Monoclonal paraproteinemia has been detected in most patients with this disorder, most commonly in the IgG/A type. The cause of scleromyxedema remains unknown. Serum of patients with the disease is able to stimulate the proliferation of fibroblasts in vitro. However, this capacity persists after removal of the IgG, which suggests that another fact, in addition to paraproteinemia, is responsible. In the presence of autologic or normal human serum, the fibroblasts of patients with scleromyxedema synthesized a higher quantity of hyaluronic acid than did those with normal fibroblasts. This suggests that the fibroblasts in these patients constitutively produce more mucine than normal fibroblasts.5
The disease mainly affects adults aged 30 to 70 years, with no predilection for either sex, and is usually chronic. Characteristic cutaneous findings are generalized papular eruption with sclerosis. The papules are firm, normochromic or erythematous in color, appearing in dense clusters.1 The lesions occur in highest frequency on the dorsal aspect of the hands and fingers, extensor surface of the limbs, and face.1 Generalized induration of the skin may result in microstomia,4 facial lesions may produce leonine facies. The disease primarily affects the skin, while systemic manifestations like proximal myopathy, inflammatory polyarthritis, esophageal dysfunction, neurologic and hematologic alterations have been described.1 When present, such manifestations appear to worsen the prognosis. Hematologic alterations are prevalent. In a series of 14 patients, monoclonal IgG paraproteinemia was apparent in 13 of them. Malignant hematologic neoplasias (multiple myeloma, acute leukemia, and T-cell lymphoma) occurred in five.5 Scleromyxedema has been reported in association with seminoma,6 6 and the association with neurologic abnormalities is also well documented.7 Symptoms like confusion, dysarthria, ascending paralysis, convulsions, and coma have been described, which usually points to a reserved prognosis. Dermato-neural syndrome has been reported on rare occasions with high triad fever, convulsions and coma with a flu-like prodome.7
Cardiac abnormalities have been described in up to 10% of cases. Autopsy data record a deposit of mucine in the middle layers of the myocardium veins and mucinous degeneration of the atheromatous plaques of the coronary veins. There are also reports of systemic arterial hypertension.8,9 In this case in particular, the patient showed gradually dilated CCI, which is why we might suppose that the clinical decompensation and diagnosis occurred at a later phase of cardiopathy. In histologic cuts, characteristically, there is hyperproliferation of fibroblasts in the dermis and abnormal deposit of mucine. The greatest alterations occurred in the upper dermis, which showed a horizontal band of mucinous material between the collagen fibers. The material is a glycosaminoglycan that is stained blue with Alcian blue in pH 2.5, and is susceptible to hyaluronidase digestion. The epidermis may appear fine due to the pressure of the mucine deposits. There is an increase of fibroblasts, which appear "plump" and starlike, and dermal fibrosis.3,5 The electron microscope reveals fibroblasts with long cytoplasmatic processes and a rough dilated endoplasmic reticulum. Moreover, numerous thin collagen fibrils, suggesting neocollagenesis, are present.
The diagnosis of scleromyxedema is based on the presence of papular lesions and characteristic sclerosis, which is a demonstration of mucine in the dermis and the presence of paraproteinemia.
In the case reported in this paper, three diagnostic criteria were made evident:
1) a quite exuberant clinical cutaneous condition, with the presence of shiny papules on the forehead, nose, glabella, which produced leonine facies. The skin showed diffuse hardening and a coarse aspect. The patient experienced reduced mobility of the hands and mouth. Systemic manifestations developed, with arthralgias in the small joints of the hands and knees, dysphasia and cardiac involvement, as well as a presence of dilated CCI and lung hypertension.
2) histology with a demonstration of amorphous material, compatible with mucine in the upper dermis;
3) IgG/A in protein immunoelectrophoresis.
Treatment of papular lesions includes intralesional hyaluronidase and triancynolone, though with scant success.9 Surgical interventions using a carbon dioxide laser and dermabrasion have been used with good cosmetic results, but they did not prevent the appearance of new lesions.10 With extensive forms, various systemic agents have been reported, showing variable effectiveness depending on the author. The use of melphalan, an alkylating agent, over long periods of time in low doses (maximum of 10 mg daily) might result in the gradual resolution of cutaneous lesions and a reduction of paraproteinemias. Nevertheless, the risk of septic and hematologic complications, in addition to neoplasias, has limited its use.5,8,9 Other chemotherapeutic agents, like cyclophosphamid, methotrexate and cyclosporine, have been used with variable results.11,12 Etretinate and isotretinoin showed variations in the results.13 There are reports of satisfactory treatment with the use of PUVA.14 Corticosteroids alone have been used by different authors, most of whom report some initial improvement followed by relapses. A purine analogue, 2-chlorodeoxyadenosine (2- CdA) has also proved effective.15 A recent study showed sustained improvement after 10 months by administering high doses of intravenous immunoglobulin. The hypothesis for the mechanism of action of this therapy is reduced production or inhibition of the circulatory action factor, which is what would be exercising a stimulatory effect on the fibroblasts.4
In the case described, the treatment was not satisfactory. The patient used melphalan, methotrexate and PUVA over a short period of time, but the lesions did no show any modifications or alterations during the course of the disease. A positive result was observed with the use of prednisone and motor physiotherapy, with an improvement of articular and oral mobility. The cardiologic condition remains compensated by conventional CCI diuretics treatment, agiotensin converting enzyme inhibitors and digitalics.
Accordingly, we conclude that the prognosis in patients with generalized scleromyxedema is limited.1 Treatment is difficult. Although different medications have proved beneficial over the short term, significant toxicity is apparent with prolonged use.
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Gladys Aires Martins
SCN Quadra 5 Bloco "A" - Torre Norte - sala 930
70715-900 Brasília DF
Tel./Fax: (61) 327-8188
Received on April 29, 2002.
Approved by the Consultive Council and accepted for publication on September 10, 2003.
* Work done at Dermatology Service of the University of Brasilia Hospital.