ARTICLE
Scleroderma-like disorders can present diagnostic difficulties since
not infrequently they imitate scleroderma to such an extent that the diagnosis
is quite arbitrary. However the causative factors and pathogenesis of
scleroderma and scleroderma-like diseases differ considerably. The familiarity
with pseudosclerodermatous diseases is of practical importance for establishing
the association with internal involvement, thus for application of an
appropriate therapy [1, 2]. One of such controversial scleroderma-like
diseases is scleromyxedema, regarded by some authors as a coexistence
of papular mucinosis and scleroderma [3].
The term scleromyxedema was coined by Gottron [4] to emphasize the clinical
similarity to scleroderma (SSc): masklike facies and sclerodactyly, and,
on the other hand, mucoid deposits in the skin. The cutaneous lesions
are composed of small, often perifollicular erythematous papules of papular
mucinosis type, not infrequently in a characteristic linear arrangement,
forming confluent plaques with marked thickening of the skin. Clinically
the folded, pendulous and thickened skin gives the impression of being
too ample, in contrast to the sclerotic skin in scleroderma, which seems
to be too tight, bound closely to the underlying tissue.
In contrast to scleroderma, histological examination
reveals abundant fibroblasts in the dermis, often also surrounding hair
follicles, with mucin deposits pushing aside the collagen bundles. A large
number of the reported cases were associated with paraproteinemia of IgG
class, mostly of lambda type, with no symptoms of myeloma [5]. Although
the disease in several instances is limited to the skin, systemic manifestations
(neurological, cardiovascular, pulmonary, renal) are not uncommon, however
usually differing from the abnormalities in SSc [5-9]. Of special significance
for differentiation from scleroderma could be a not-infrequent central
nervous system involvement, sometimes acute psychosis [3, 10].
The disease is easily recognized, although in some longlasting cases
skin indurations may be as pronounced as in diffuse scleroderma with sclerodactyly,
masklike facies, esophageal involvement, myositis, etc. [7, 11]. Vascular
changes, mainly of atherosclerosis type, might cause hyperesthesia and
paresthesia of the limbs, mimicking Raynaud's phenomenon. However the
course of the disease, with possible spontaneous resolution, the type
of systemic involvement, and the therapies differ considerably from scleroderma.
In spite of some reports of good results with the therapies also used
in scleroderma: cyclophosphamide [12], corticosteroids [10] and melphalan
[13], all these treatment modalities are frequently disappointing. However,
in our experience intravenous immunoglobulins proved to be highly effective,
especially in cases associated with paraproteinemia. Therefore the differentiation
between scleromyxedema and systemic scleroderma is of practical significance,
and is both necessary and feasible.
The patients
We observed 4 cases of scleromyxedema with advanced skin sclerosis:
2 males and 2 females, followed-up for several, up to more than ten, years.
Overall, sclerosis developed progressively, with striking similarity to
scleroderma, however without osteolysis and the visceral involvement characteristic
of SSc.
In the first patient, a male, 53-year-old, in whom the disease started
10 years previously, the skin of the trunk was thickened and typically
folded, in spite of pronounced sclerodactyly and sclerosis of the face
(Fig. 1a, b). The second
patient, a male, 56-year-old, had widespread cystic lesions on the face
and ears, an important sign, of diagnostic significance (Fig.
2). In both patients paraproteinemia was of IgG lambda type, revealed
in the second case several years after the onset of the disease.
The third patient, a 42-year-old female,
in whom the erythematous lesions had appeared at the age of 29 years and
skin sclerosis at the age of 32 years, was previously recognized and treated
as diffuse SSc in spite of masklike facies with ectropion and elevated,
skin-colored papules and cysts on the forehead (Fig.
3a, b). She complained of swallowing difficulties, but esophagus
did not show abnormal peristalsis. She had also moderate myositis confirmed
by electromyography. No paraproteinemia was detected within 10 years of
her illness.
In the fourth patient, a female 62-year-old, sclerotic changes present
for 7 years involved the whole trunk, facies and hands, with nodules characteristic
of scleromyxedema in the retroauricular area. For one year she had also
myositis confirmed by quantitative EMG, histology and high levels of CPK.
The therapy with corticosteroids was only effective for the muscle involvement
but did not affect the cutaneous lesions. Also in this patient, paraproteinemia
was not revealed within 7 years of illness.
In all four patients skin biopsies showed proliferation of fibroblasts
and mucin deposits in the dermis positive for Alcian blue stain 2.5 pH
and almost negative after digestion with hyaluronidase (Fig.
4).
Comment
The clinical similarity of all our patients to scleroderma was quite
striking, however there were no vascular changes, and sclerodactyly with
no osteolysis and digital ulcers was secondary to the fibrosis. Histopathology
showed proliferation of fibroblasts and mucin deposition, whereas in scleroderma
sclerosis of the connective tissue stroma is due to compact collagen bundles
and is preceded by inflammatory and vascular changes. Sera of patients
with scleromyxedema stimulate fibroblast proliferation [14], but not the
glycosaminoglycan synthesis [15], whereas mucin appears to be produced
mainly locally by fibroblasts. Also the internal involvement in scleromyxedema
is due to mucopolysaccharide (mainly hyaluronic acid) deposition between
interweaving bundles of spindle shaped fibroblasts and thick collagen
bundles, while in scleroderma there is no proliferation of fibroblasts.
Nevertheless some clinical signs, e.g. pulmonary hypertension,
restrictive pulmonary disease and decreased motility of the esophagus
might be indistinguishable. The fatal case described as coexistence of
scleromyxedema and kidney scleroderma [10] showed renal glomerular changes
characteristic of scleroderma. However, at autopsy no signs of scleroderma
were disclosed in internal organs. The patient had uncontrolled hypertension
and acute psychosis which could be related to hypertension since no pathological
brain changes were revealed at the autopsy. It should be stressed that
pathological features of the kidney in malignant hypertension may display
a striking similarity to scleroderma kidney [16]. Therefore the pattern
of renal changes may not be decisive in the differentiation between scleroderma
and hypertension. In a case also recognized as the coexistence of papular
mucinosis and scleroderma [3] slight cutaneous changes at the onset of
the disease were accompanied by psychic disturbances. Raynaud's phenomenon
with capillaroscopic abnormalities, some dilatation of the esophagus and
ANA of speckled pattern and unknown specificity were interpreted as compatible
with scleroderma. However clinical and histological features were characteristic
of scleromyxedema. Importantly, both central nervous system involvement
and a mild course would favor the diagnosis of scleromyxedema with pronounced
sclerodermatous changes. Even in cases mimicking scleroderma the main
pathological process remains unchanged: proliferation of stellate fibroblasts,
mucin deposition in the skin, sometimes also in internal organs and in
the vessel walls.
Paraproteinemia without symptoms of myeloma is a most characteristic
finding although not present in all cases. The skin morphology and pathology,
the type of visceral involvement, if present, association with monoclonal
protein in the majority of cases, a possible central nervous system involvement,
a chronic unpredictable course of the disease with reported spontaneous
remissions [17, 18] provide the basis for differentiation from scleroderma.
Thus scleromyxedema should be regarded as a separate entity with more
or less pronounced scleroderma-like features.
REFERENCES
1. Jablonska S, Blaszczyk M. Differential diagnosis of scleroderma-like
disorders. In: Clements PJ, Furst DE, eds. Systemic sclerosis.
Baltimore: Williams and Wilkins, 1995: 99-120.
2. Jablonska S, Blaszczyk M. Scleroderma-like disorders. Sem Cutaneous
Med Surg 1998; 17: 65-76.
3. Sawada Y, Seishima M, Funabashi M, Noda T, Maeda M, Kitajima Y. Papular
mucinosis associated with scleroderma. Eur J Dermatol 1998; 8:
497-500.
4. Gottron HA. Skleromyxedem (eine eigenartige Erscheinungsform von
Myxothesaurodermie). Arch Dermatol 1954; 199: 71-91.
5. Harris AO, Altman AR, Tschen JA, Wolf JE. Scleromyxedema: report
of two cases and review of the literature. Int J Dermatol 1989;
28: 661-7.
6. Verity MA, Toop J, McAdam LP, Pearson CM. Scleromyxedema myopathy:
histochemical and electron microscopic observations. Am J Clin Pathol
1978; 69: 446-51.
7. Fudman EJ, Golbus J, Ike RW. Scleromyxedema with systemic involvement
mimics rheumatic diseases. Arthritis Rheum 1986; 29: 913-7.
8. Gabriel SE, Perry HO, Oleson GB, Bowles CA. Scleromyxedema: a scleroderma-like
disorder with systemic manifestations. Medicine 1988; 67: 58-65.
9. Goodby A, Bergstresser PR, Chaker B, Pandya AG. Fatal scleromyxedema:
report of a case and review of the literature. J Am Acad Dermatol
1998; 38: 289-94.
10. Kantor GR, Bergfeld WF, Katzin WE, Reynolds OD, Biscardi AP, Lobur
DM, et al. Scleromyxedema associated with scleroderma renal disease
and acute psychosis. J Am Acad Dermatol 1986; 14: 879-88.
11. McAdam LP, Pearson CM, Pitts WH, Sadoff L, Verity MA. Papular mucinosis
with myopathy, arthritis, and eosinophilia: a histopathologic study. Arthritis
Rheum 1977; 20: 989-95.
12. Howsden SM, Herndon JH Jr, Freeman RG. Lichen myxedematosus: a dermal
infiltrative disorder responsive to cyclophosphamide therapy. Arch
Dermatol 1975; 111: 1325-30.
13. Harris RB, Perry HO, Kyle RA, Winkelmann RK. Treatment of scleromyxedema
with melphalan. Arch Dermatol 1979; 115: 295-9.
14. Harper RA, Rispler J. Lichen myxedematosus serum stimulates human
skin fibroblast proliferation. Science 1978; 188: 545-7.
15. Ferrarini M, Helfrich DJ, Walker ER, Medsger TA, Whiteside TL. Scleromyxedema
serum increases proliferation but not the glycosaminoglycan synthesis
of dermal fibroblasts. J Rheumatol 1989; 16: 837-41.
16. Jablonska S. Scleroderma and Pseudoscleroderma. Warsaw :
Polish Med Publ, English edition (Dowden Hutchinson Ross Inc. Stroudsburg
Pa), 1975.
17. Hardie RA, Hunter JAA, Urbaniak S, Habeshaw JA. Spontaneous resolution
of lichen myxoedematosus. Br J Dermatol 1979; 100: 727-30.
18. Boffa MJ, Ead RD. Spontaneous improvement of scleromyxedema. Clin
Exp Dermatol 1995; 20: 157-60.
|
Version imprimable
