ARTICLE
Auteur(s) : Guan-Yu Chen1, Ming-Fei
Liu2, J Yu-Yun Lee3, WenChieh Chen4
1Department of Dermatology, Armed Forces Taichung
General Hospital, 348, Sec. 2, Chung-Shan Road, Tai-Ping, Taichung
411, Taiwan
2Department of Rheumatology College of Medicine,
National Cheng Kung University, 138 Sheng-Li Road, 704 Tainan,
Taiwan
3Department of Dermatology, College of Medicine,
National Cheng Kung University, 138 Sheng-Li Road, 704 Tainan,
Taiwan
4Department of Dermatology, Chang Gung University, Chang
Gung Memorial Hospital, Kaohsiung, Ta-Pei Road 123, Niao-Sung, 833
Kaohsiung, TaiwanFax: (+886) 7 7318762.
accepté le 9 Août 2004
Cutaneous mucinosis, characterized by mucin deposits in the dermis
[1], involves a heterogeneous group of disorders, which can be
broadly divided into two groups: (I) primary cutaneous mucinosis
exhibiting distinctive clinical and pathological characteristics
such as scleredema, pretibial myxedema and (II) secondary cutaneous
mucinosis associated with various diseases such as lupus
erythematosus and dermatomyositis, presenting as a non-distinctive,
incidental histopathological feature [2]. Cutaneous mucinosis as a
clinically frank skin lesion preceding dermatomyositis is unusual.
Here, we report cellulitis-like massive cutaneous mucinosis in a
young female shortly before full-blown development of
dermatomyositis. The patient also subsequently acquired large
punch-out ulcers and vesiculobullous lesions. In spite of
aggressive treatment with steroid pulse therapy, she died 9 months
after disease onset, probably due to a complication of intestinal
vasculopathy. The combination of mucinosis, dermatomyositis,
pyoderma gangrenosum-like ulceration, subepidermal vesiculobullous
formation, and fatal intestinal vasculopathy seems to represent a
distinct syndrome.
Case report
A 21-year-old Taiwanese woman was seen in May 2002 with a large
painful erythematous, indurated, cellulitis-like mass extending
from the right lower abdomen, across the major labia to inner thigh
over the previous 3 weeks ( (figure 1A,B) ). Physical
examination additionally revealed malar rash, violaceous
infiltrated plaques over bilateral ears and periungual
telangiectasia ( (figure
1C ) and D), without lymphadenopathy and muscle weakness.
There was past history of leukopenia and thrombocytopenia one year
previously. Results of serological examination including ANA,
anti-dsDNA, anti-ENA panels, VDRL, and erythrocyte sedimentation
rate were all unremarkable. Abnormal laboratory values included
mild leukopenia (3.0 K/cmm, normal: 3.8-9.8), significant
thrombocytopenia (87 K/cmm, normal: 140-440), hypoalbuminemia (2.8
g/dl, normal: 3.6-5.0) and elevated SGOT (143 U/l, normal: 5-40).
Histopathology of the skin specimen taken from the right lower
abdomen showed an atrophic epidermis with vacuolar alteration of
basal keratinocytes and interstitial mucin deposits with patchy
perivascular lymphocytic infiltrate in the dermis as well as
subcutaneous tissue ( (figure 2A,B,C) ).
Histopathology from the left ear revealed vacuolar alteration and
occasional necrosis of basal cells and superficial and deep
perivascular and periadnexal lymphocytic infiltrate. Direct
immunofluorescence showed deposition of IgM and C3 within cytoid
bodies along the dermo-epidermal junction ( (figure 2D) ). The changes
were consistent with lupus erythematosus and dermatomyositis. The
tentative clinical diagnosis was an undefined collagen vascular
disease, and oral prednisolone (25 mg/day) and hydroxychloroquine
(200 mg/day) were initiated.
Incapacitated muscle weakness and generalized edema rapidly
developed in three weeks with the appearance of heliotrope
erythema, Gottron’s papules and a high serum level of creatine
kinase (9,794 IU/l, normal: 20-170 IU/l). Electromyography showed
typical changes like polyphasic waves with a small amplitude, short
duration and early recruitment, indicating myopathy. Diagnosis of
dermatomyositis was established, and a further systemic survey
excluded association with internal malignancy. Intravenous
methylprednisolone (60 mg/day) was administrated for one month
during which time the serum creatine kinase decreased from 9,794 to
1,582 IU/l. However, muscle weakness progressed with the
development of dysphagia and dysphonia. Steroid pulse therapy with
methylprednisolone (1 gm/day) was given once daily for 3
consecutive days. The clinical course was complicated by two
episodes of aspiration pneumonia, necessitating antibiotic therapy
and reduction of the dose of methylprednisolone, gradually tapered
to 40 mg/day in three months. The serum creatine kinase level was
92 IU/l. Tarry stool with occult stool blood (+++) was observed
upon maintenance of steroid therapy.
One deep punched out ulcer (12 × 6 cm2) rapidly
developed in two months on the right lower abdomen, where a biopsy
was taken previously. Histopathological examination of the ulcer
revealed extensive ischemic necrosis of the dermis and subcutaneous
tissue without calcification or fungal infection. The lumen of a
large subcutaneous vein was partially occluded by fibrin ( (figure 3A,B) ).
Superimposed infection with E. coli & Klebsiella pneumoniae was
identified in tissue culture. The ulcer healed almost completely
within two months treated with 1% chloramphenicol ointment. In
December 2002, several vesicles and bullae occurred on four
extremities, especially in the skin areas of steroid-induced striae
distensae. Marked dermal edema with a slight deposition of mucin in
the papillary dermis was observed histopathologically, without
significant findings in direct immunofluorescence.
On January 1 2003, the patient suffered from another episode of
aspiration pneumonia and respiratory failure, she was intubated and
transferred to the intense care unit (ICU). There was profound
muscle weakness with muscle power at grade 2, whereas creatine
kinase still remained within normal limits. Because of carbon
dioxide retention, involvement of respiratory muscles was
suspected. On January 15 2003, she presented with abdominal
fullness, diffuse tenderness and hardness of the abdominal wall
with hypoactive bowel sound. Computed tomography scan showed
massive ascites and diffuse bowel wall thickening, suggestive of
vasculitis-related bowel ischemia ( (figure 4) ). The condition
rapidly went downhill in one week and an urgent exploratory
laparotomy disclosed a large amount of ascites and severe diffuse
inflammation of the intestine and mesentery without evidence of
perforation. Her condition worsened after the operation,
complicated with sepsis, disseminated intravascular coagulation,
pleural effusion, empyema, jaundice and continuing drainage of
bloody ascites. In spite of intensive treatment with highly potent
antibiotics and massive blood transfusion, the patient expired on
February 3 2003, 9 months after the initial expression of
cellulitis-like massive cutaneous mucinosis (( figure 5 )).
Discussion
Our case is unique in that (I) appearance of cellulitis-like
massive cutaneous mucinosis at the very beginning, in advance of
the full-blown dermatomyositis; (II) recalcitrant course of the
disease with only a brief response to high-dose steroids; (III)
extremely high titers of serum creatine kinase but negative
serological findings related to connective tissue disease; (IV)
multifaceted cutaneous manifestations including massive gross
mucinosis, large deep pyoderma gangrenosum-like ulceration, and
extensive bullous formation; (V) rapid mortality probably due to
vasculitis involving intestinal tract. The diagnosis of
dermatomyositis in our case was established following the criteria
described by Boghan and Peter [3]. Cutaneous lesions of
dermatomyositis may precede, simultaneously occur, or follow the
onset of muscle weakness [4]. The histological demonstration of
mucin deposits in cutaneous lesions of dermatomyositis is common,
but these deposits usually do not have macroscopic relevance [5].
Cutaneous mucinosis associated with dermatomyositis might manifest
as scleromyxedema, corrugated plaque on the abdominal wall, papular
mucinosis, reticular erythematous mucinosis and plaque-like
mucinosis [5]. In a review of seven cases of
dermatomyositis-associated macroscopic mucinosis, female
predominance (6/7) was found with age ranging between 41 and 66
years, and duration of symptoms before definite diagnosis lying
between 4 and 24 months [1, 5-7]. Proximal muscle weakness was
present in all patients, with the level of creatine kinase between
195 and 1641 IU/l. Three patients were positive for ANA.
Examination of anti-ENA panels, direct immunofluorescence and
internal malignancy all showed negative results. The duration of
treatment was age-dependent, and all of the patients were well
controlled on low-dose prednisolone. In these patients, cutaneous
lesions of mucinosis appearing at the early stages of the disease
seemed to be associated with a good response to treatment [5],
which was in contrast to our patient.
Nearly 90% of patients with dermatomyositis have some
autoantibodies [8], with elevated ANA levels being found in 60 to
80% of dermatomyositis/polymyositis [9]. Although systemic lupus
erythematosus is associated with polymyositis in 4-16% of cases
[10] and our patient expressed some characteristic cutaneous
features of lupus erythematosus, the lack of serological evidence
of specific autoantibodies is insufficient to reach the diagnosis
of lupus erythematosus or overlap syndrome. On the other hand,
serological evaluation of 21 children with juvenile
dermatomyositis, at age onset before 18 years [11], revealed
negative ANA and negative anti-ENA in 90.5% and 100% of patients,
respectively [12]. They were mostly female with acute onset and
appearance of malar rash, vasculopathy and more systemic
involvement [13]. In a retrospective analysis of 35 dermatomyositis
patients by Jones et al. [14], six of the patients with markedly
elevated levels of serum creatine kinase, up to 11,600 IU/l, had
developed an occult malignancy. However, no malignancy was
identified in our case in spite of the extremely high titers of
serum creatine kinase.
Rapid development of large deep pyoderma gangrenosum-like
ulceration in our patient is distinctive. Typical features of
pyoderma gangrenosum were, however, absent in the histopathology of
the ulceration. On the other hand, concurrence of dermatomyositis
and pyoderma gangrenosum is very unusual [15]. Vesiculobullous
formation in dermatomyositis is also rare and was proposed to be
associated with the existence of an internal malignant process,
especially gynecologic malignancies [16]. Since the direct
immunofluorescence study on the reported cases [16] as well as ours
failed to reveal any deposition of immunoglobulin in the basement
membrane zone, these subepidermal vesicles were most likely caused
by marked dermal edema rather than through immunological
process.
The fatal intestinal perforation in our patient seemed to be
most likely caused by serious vasculitis, which was evidenced by
the findings of (I) large deep cutaneous ulcer with
histopathological changes of necrotic vasculopathy, (II) tarry
stool, hematemesis, bloody stool, and bloody ascites probably due
to gastrointestinal perforation, (III) diffuse bowel wall
thickening demonstrated in computed tomography scan, suggestive of
vasculitis-related bowel ischemia. Radiologic findings in various
types of vasculitis often overlap considerably and therefore have
limited value in making a specific diagnosis [17]. Vasculitis
involving gastrointestines should be considered whenever mesenteric
ischemic changes occur in young patients, are noted at unusual
sites (e.g., stomach, duodenum, rectum), and have a tendency to
concomitantly involve the small and large intestine [17]. Severe,
occlusive damage often leading to ischemia may result in ulceration
and perforation, which is more commonly seen in Henoch-Schönlein
purpura, polyarteritis nodosa, microscopic polyangiitis, Wegener’s
syndrome and Churg-Strauss syndrome [18]. All of these can be ruled
out by (I) no clinical manifestation of palpable purpura,
hypertension or asthma, (II) no IgA deposition on vessel wall in
immunohistochemistry, (III) serological absence of eosinophilia,
C-antineutrophilic cytoplasmic antibody (C-ANCA) or
P-antineutrophilic cytoplasmic antibody (P-ANCA). Finally,
adult-onset dermatomyositis complicated with life-threatening
gastrointestinal ischemia and perforation was very rare [19].
Supposedly, a triggered inflammatory process led to changes in the
endothelium of small arteries and capillaries accompanied by
thrombosis formation and vessel obliteration, causing tissue
ischemia and necrosis [20].
To summarize, the young female patient in our case presented a
syndrome-like manifestation with concurrence of cellulitis-like
massive cutaneous mucinosis, dermatomyositis with negative titer of
ANA but high titer of serum creatine kinase, rapidly progressive
deep punch-out ulcer, vesiculobullous formation, and fatal
intestinal vasculopathy. The intractable course and the grim
prognosis of this rare combination warrant further attention.
Differentiation to adult-onset juvenile dermatomyositis should be
considered.
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