ARTICLE
Papular mucinosis (scleromyxedema/lichen myxedematosus) is a rare disease
characterized by a symmetric distribution of erythematous to yellowish
papules and/or papules, most commonly involving the face, neck and arms
[1] accompanied by diffuse skin thickening in some cases. In the diffuse
sclerotic variant, some authors exclusively reserve the term "scleromyxedema"
in light of its clinical resemblance to systemic scleroderma [2].
Some cases of papular mucinosis are associated with systemic diseases
such as paraproteinaemia [3, 4], systemic lupus erythematosus [5-7], non-Hodgkin's
lymphoma [8], hypothyroidism [9] and myopathy [1]. The association of
scleroderma with papular mucinosis has been rarely reported [10, 11].
Scleroderma fibroblasts synthesize more collagen than those from normal
subjects [12]. The cause of this excessive production of collagen in scleroderma
is unknown; both intrinsic overactivity and excessive stimulation of fibroblasts
may occur [13]. Mucin deposits are also found in the dermis of scleroderma
patients [14]. In this report, we describe a rare and interesting case
of papular mucinosis associated with scleroderma.
Case report
A 49-year-old Japanese woman developed Raynaud's phenomenon in December
of 1989. When she visited our hospital in September of 1994, slight swelling
and mild sclerodactyly in her fingers, induration of the lingula, and
facial edema were observed. However, her condition at that time did not
satisfy the criteria for scleroderma proposed by Barnett and Conventry
[15] and LeRoy et al. [16]. Since a diagnosis of endogenous depression
had been made by a psychiatrist, she had been treated with etizolam (1
mg/day), amitriptyline hydrochloride (20 mg/day) and sulpiride (200 mg/day).
She had never been exposed to environmental factors such as tryptophan,
organic solvents and aliphatic hydrocabons. Since May 1996, the Raynaud's
phenomenon had exacerbated and the fingers showed a sausage-like appearance
(Fig. 1). Multiple, elevated,
asymptomatic, skin-colored papules on the dorsal regions of hands were
also observed. The number of these papules gradually increased. Blood
cell counts, laboratory data on liver and renal function were all within
normal limits. Serum protein immunoelectrophoresis demonstrated a mild
polyclonal IgG hypergammaglobulinemia (1,940 mg/dl, normal range = 650-1,600
mg/dl), while the levels of IgA and M were within normal ranges. The titer
of antinuclear antibody was 1:1,280 in a speckled pattern, whereas anti-RNP
antibody, anticentromere antibody, anti-Scl-70 antibody, anti-SS-A antibody,
anti-SS-B antibody and anti-Sm antibody were all negative. No abnormality
was found on chest X-ray and ECG. Capillaroscopical findings of the cuticle-proximal
nailfolds showed the dilatation and partial absence of the capillary loops
of proximal nailfolds [17]. A barium swallow test revealed a dilatation
of the upper and middle parts of the esophagus. Anti-thyroid and anti-microsomal
antibodies were weakly positive with titers of 1:80 and 1:20, respectively;
the levels of T3, T4 and TSH were within normal
ranges.
Histological findings for the papules on the
dorsal regions of her right hand showed a perivascular lymphocytic infiltrate
within the superficial dermis, accompanied by sclerosis and a striking
deposition of mucin in the mid and lower dermis (Fig.
2). The abundant deposited substance was positive for alcian blue
(pH 2.5) stain (Fig. 3),
but negative for alcian blue (pH 2.5) stain following digestion by hyaluronidase,
alcian blue stain (pH 1.0) and PAS stain. The substance showed a diffuse
metachromatic staining pattern with toluidine blue stain at pH 4.0 and
7.0 but not at pH 2.0. These findings suggested that the mucinotic material
contained hyaluronic acid. On the other hand, the skin from the dorsal
aspect of her left forearm showed slightly thickened collagen fibers with
mild mucinosis in the dermis. A diagnosis of papular mucinosis associated
with scleroderma type I was made, the latter according to the criteria
of Barnett and Coventry [15]. The patient also satisfied the criteria
for the limited cutaneous systemic sclerosis type according to the classification
scheme of LeRoy et al. [16].
She received treatment with prostaglandin E1 derivatives,
10 µg, intravenously every day for 2 months. The papules have diminished
in size and her sclerodactyly has become less prominent, suggesting the
effectiveness of prostaglandin E1 derivatives in this case.
Discussion
Cutaneous mucinosis is a heterogenous group of disorders characterized
by an accumulation of mucin in the dermis (Table
I). The pathogenesis may be related to various disorders, such
as metabolic or collagen-vascular disease and paraproteinemia [18]. A
lichenoid eruption with discrete papules is localized or generalized in
papular mucinosis/lichen myxedematosus [2]. On the other hand, the confluent
papular and sclerotic form is observed in scleromyxedema, where diffuse
thickening of the skin underlies the papules. An unusual form of cutaneous
mucinosis, acral persistent papular mucinosis, has been reported [19-21].
It is characterized by multiple, discrete papules located symmetrically
on the back of the hands, wrists and distal forearms; focal mucin deposits
in the upper dermis are seen [21]. It is unclear as to whether acral persistent
papular mucinosis is a distinct entity or a variant of the papular form
of lichen myxoedematosus/scleromyxedema, i.e. papular mucinosis
[20]. This current case showed similar clinical findings to this type
of cutaneous mucinosis. Its uniqueness lies in an association with limited
cutaneous scleroderma. Scleromyxedema, which is the generalized lichenoid
papular variant of papular mucinosis [22], is characterized by papules
with diffuse thickening of the skin similar to scleroderma. Because sclerodactyly
and Raynaud's phenomenon were clearly observed in this case, the diagnosis
of papular mucinosis with scleroderma was made.
It is well known that collagen fibers are impaired
and collagen synthesis is enhanced in scleroderma fibroblasts [23, 24],
and the mRNA levels of procollagen increase in scleroderma fibroblasts
compared with normal fibroblasts [25-27]. Furthermore, scleroderma fibroblasts
have a disturbed interaction with collagen fibers [28]. However, the aetiology
of scleroderma has not been completely defined. Mucin deposits are found
in the dermis, mainly in the deep reticular dermis and interlobular septa
in patients with scleroderma and morphea [14, 29, 30]. The mucin deposits
localize to areas of sclerosis [29] and may be among the earliest histological
findings in scleroderma [30]. It may be reasonably speculated that in
some instances papular mucinosis may represent a special form of scleroderma
associated with prominent if not dominant mucin production. In the patient
with papular mucinosis associated with systemic lupus erythematosus, enhanced
glycosaminoglycan production is observed in both normal and the patient's
fibroblasts when incubated with the patient's serum [7].
Since the serum from patients with papular mucinosis stimulates DNA
synthesis and proliferation of fibroblasts [31], some unknown serum factors
may be involved in the pathogenesis of the mucinosis and sclerosis seen
in this disorder.
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