ARTICLE
Auteur(s) : Mutsuko Ehara, Takashi Oono, Osamu
Yamasaki, Hironori Matsuura, Keiji Iwatsuki
Department of Dermatology, Okayama University School of
Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1
Shikata-cho, Okayama, 700-8558, Japan
accepté le 28 Decembre 2005
Generalized morphea-like systemic sclerosis (GM-like SSc), first
described by Yamakage and Ishikawa [1], is a variant of systemic
sclerosis (SSc) that is characterized by symmetrically-distributed
morphea-like lesions. In addition to clinical features suggestive
of SSc, these patients usually have sclerotic plaques on the upper
arms, lateral forearms, lumbar area, and back. Some patients may
have a history of exposure to organic solvents [2, 3]. Recently, we
treated two female patients who had morphea-like plaques located
mainly on the body surfaces compressed by underclothes.
Case report
Case 1
On December 8, 1999, a 70-year-old woman visited our clinic because
of erythematous plaques located on the anterior chest. Her past
history included a hysteromyotomy at the age of 38 years. After the
operation, she developed edema of the lower legs that was
associated with proteinuria and was successfully treated by diet
alone. In January 1998, however, the patient’s leg edema recurred
together with proteinuria, and she was diagnosed as having
membranous glomerulonephritis. Her symptoms resolved with bed rest
and diet. In 1993, the patient first noticed the occurrence of
Raynaud’s phenomenon; positive autoantibodies against centromere
antigens were found. She was given a tentative diagnosis of
systemic sclerosis without having exhibited any sclerotic cutaneous
lesions, and she was treated with tocopherol nicotinate and
beraprost sodium. However, in September 1999, erythematous patches
occurred on the patient’s anterior chest, extending over the
abdomen and shoulders.
On the first visit, palm-sized, brownish erythematous plaques
were present in a symmetrical fashion on the anterior chest and
abdomen. Some of the lesions showed an annular form with central
pigmentation and a reddish border, suggestive of morphea. One year
later, the eruptions on the anterior chest coalesced to form
well-demarcated, pigmented sclerotic lesions with inflammatory
borders. The lesions were located in the skin areas compressed by
underclothes (figure
1A). The abdominal lesions became diffusely sclerotic with
brownish pigmentation. No telangiectatic lesions were observed on
the lips, palms, and dorsa of the hands, and there was no
sclerodactyly or ankyloglossia. The patient had no pulmonary or
gastrointestinal symptoms including dysphagia and pyrosis.
In biopsy specimens taken from an erythematous plaque located on
the left shoulder, nodular or thick collagen bundles were noted in
the entire dermis. Inflammatory cell infiltrates mainly composed of
lymphocytes were observed around the dermal blood vessels and sweat
glands. The infiltrates were also present in the interstitial
spaces of the dermis. Laboratory tests found positive
anti-centromere antibodies (1: 1280); there were no antibodies to
nuclear components, including ribonucleoprotein, topoisomerase 1,
single- or double-stranded DNA, and Sm antigens. Blood chemistry
tests showed no abnormalities except for a slightly elevated γ-GTP
level at 90 U/L (normal value, < 60 U/L). Proteinuria and
microscopic hematuria persisted due to the patient’s pre-existing
mild glomerulonephritis. No abnormalities were found on chest
X-ray, electrocardiogram, and respiratory function tests.
Based on the typical clinical and histologic findings, taken
together with the presence of Raynaud’s phenomenon and
anti-centromere antibodies, the patient was diagnosed as having
GM-like SSc. With topical steroid and topical PUVA therapy, once or
twice a week, the patient’s abdominal sclerosis became soft;
finally, only a brownish pigmentation was left. The chest lesions
also responded to this treatment regimen, but the sclerotic changes
remained.
Case 2
A 57-year-old Japanese woman was referred to our clinic complaining
of sclerotic plaques with pigmentation. At the age of 33 years, she
underwent an operation for placental separation, and developed
post-transfusion hepatitis. She had been working as a sign painter
for 20 years, and exposed to thinner containing organic solvents,
such as toluene and esters, for at least 10 years. Her family
history was not contributory. In September 2003, she noticed
pigmented sclerosis on the abdominal region. Similar lesions
occurred on the anterior chest and extensor surfaces of the lower
legs. She had no systemic complaints such as pulmonary and
gastrointestinal symptoms.
On examination, the patient presented with brownish, sclerotic
lesions on the anterior chest, shoulder, and back, the distribution
of which conformed to the shape of the brassiere that she wore
(figure 1B).
Diffuse sclerosis on the abdomen corresponded to the areas
compressed by her underpants. The lesions on her anterior legs were
located on the areas mechanically compressed by sitting on the
floor in the Japanese manner.
Skin biopsy specimens taken from the abdomen showed thick
collagen bundles in the entire dermis. A mild inflammatory cell
infiltrate was observed around the blood vessels in the superficial
dermis (figure
1C). Routine laboratory testing showed that the complete
blood cell count was normal, and blood chemistry tests were normal.
No antibodies against nuclear antigens, including the centromere,
topoisomerase 1, ribonucleoproteins, and single and double-stranded
DNA, were found.
In addition to the presence of symmetrically-distributed
sclerotic plaques and diffuse sclerosis on the abdomen, the patient
had a long-term history of exposure to organic solvents. Therefore,
we tentatively diagnosed her as having GM-like SSc and carefully
followed her for the appearance of further symptoms, such as
Raynaud’s phenomenon. The sclerotic lesions improved gradually with
topical steroid, oral tranilast 300 mg/day, and the avoidance of
compression by underclothes.
Discussion
Both patients presented with morphea-like plaques with inflammatory
borders. Although the cutaneous lesions were indistinguishable from
those of GM, the lesions were distributed symmetrically, and
diffuse, pigmented sclerosis, as is often observed in patients with
SSc, was present on the lower abdomen. Furthermore, in contrast to
the usual presentation of GM, case 1 had Raynaud’s phenomenon and
anti-centromere antibodies, similar to the previously reported
cases of GM-like SSc [4]. Concurrent SSc and morphea also needs to
be ruled out. The skin lesions in GM-like SSc are
well-circumscribed sclerotic plaques with erythema. Skin lesions
observed in our patients were compatible with those of GM-like SSc.
Recently, yet another differential diagnosis, the skin lesions seen
in nephritic fibrosing dermopathy (NFD), has been reported. The
skin lesions of NFD consist of ivory colored plaques. The
histological findings of NFD include increased numbers of dendritic
cells and elastic fibers [5]. Serological findings, such as
anti-topoisomerase antibody, and anticentromere antibodies are also
important in the differential diagnosis. While case 1 had
membranous glomerulonephritis, the clinical and histological
findings excluded the diagnosis of NFD. Case 2 had a 10-year
history of exposure to organic solvents, which are known to be
causative factors for the development of occupational GM-like SSc
[2].
It is intriguing to note that the cutaneous lesions in both
patients were confined to areas mechanically compressed areas by
underclothes. In case 2, the shape of the sclerotic lesions on the
anterior chest and back corresponded to the shape of the patient’s
brassiere. Previous reports have stated that mechanical pressure
and organic compounds can induce the generation of cell growth
factors and cytokines from fibroblasts and endothelial cells [6-8].
These may in turn promote collagen synthesis and inflammation that
leads to sclerosis. Skin lesions can be induced by many
environmental stresses, such as scratching and local pressure,
manifesting as the Koebner phenomenon. The pathophysiology of the
Koebner phenomenon is still unclear, though the mechanism may
involve the release of local cytokines. Cytokines, such as
TNF-alpha and IL-6, have been found in local cells affected by
trauma and scratching. IL-6 is also increased in the serum of SSc
patients. Based on these findings, we postulated that local
pressure by underclothes induced the sclerotic lesions in our two
patients. Desruelles et al. have reported that multiple morphea
lesions were induced by the Koebner phenomenon [9]. Therefore,
local compression by underclothes, as a manifestation of the
Koebner phenomenon, might be responsible for the development of
GM-like lesions in patients with subclinical SSc.
Acknowledgements
We would like to thank medical students M. Senda, Y.Takahashi,
M.Tanaka, S. Tamada, and K. Hashimoto for helping with the
manuscript and figures.
References
1 Yamakage A, Ishikawa H, Saito Y, et al.
Occupational Scleroderma-Like Disorder Occurring in Men Engaged in
the Polymerization of Epoxy Resins. Dermatologica 1980; 161: 33-44.
2 Yamakage A, Ishikawa H. Generalized Morphea-Like
Scleroderma Occurring in People Exposed to Organic Solvents.
Dermatologica 1982; 165: 186-93.
3 Ishikawa O, Warita S, Tamura A, et al.
Occupational scleroderma. A 17-year follow-up study. Br J Dermatol
1995; 133: 786-9.
4 Sumi K, Yamamoto T, Yokozeki H, et al.
Amyloid deposition associated with generalized morphea-like
scleroderma. Eur J Dermatol 2003; 13: 509-11.
5 Swartz RD, Crofford LI, Phan SH, et al.
Nephrogenic fibrosingdermopathy: a novel cutaneous fibrosing
disorder in patients with renal failure. Am J Med 2003; 114:
563-72.
6 Mori Y, Ishida W, Bhattacharyya S, Li Y,
et al. Selective inhibition of activin receptor-like kinase 5
signaling blocks profibrotic transforming growth factor beta
responses in skin fibroblasts. Arthritis Rheum 2004; 50(12):
4008-21.
7 Leask A, Denton CP, Abraham DJ, et al.
Insights into the molecular mechanism of chronic fibrosis: the role
of connective tissue growth factor in scleroderma. J Invest
Dermatol 2004; 122(1): 1-6.
8 Ihn H, Yamane K, Kubo M, et al. Blockade
of endogenous transforming growth factor beta signaling prevents
up-regulated collagen synthesis in scleroderma
fibroblasts:association with increased expression of transforming
growth factor beta receptors. Arthritis Rheum 2001; 44(2):
474-80.
9 Desruelles F, Castanet J, Botcazou V,
Lacour JP, Ortonne JP. Koebner phenomenon and multiple
morphea. Ann Dermatol Venereol 1998; 125: 604.
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