Anti-p155/140 antibody-positive dermatomyositis with metastasis originating from an unknown site.
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ABSTRACT: Idiopathic inflammatory myopathies (IIMs) are chronic systemic autoimmune diseases characterised by symmetrical, proximal muscle weakness. Dermatomyositis represents one subset of IIMs, in which skin rashes are present in addition to muscle weakness. Myositis-specific antibodies can only be detected in myositis, and they are directed against specific proteins found in the cytoplasm or in the nucleus of cells. With this case-based article, we introduce the recently detected anti-TIF1γ, anti-NXP2, anti-SAE and anti-MDA5 antibodies that form various clinical groups. These antibodies could be detected in patients with dermatomyositis. The myositis-specific autoantibodies of three hundred and thirty-seven Hungarian patients with IIM were detected. Retrospective analysis of the clinical findings has also been introduced by revision of the medical history. We had twelve patients with anti-TIF1γ positivity, four patients with anti-NXP2 positivity and four patients with anti-SAE positivity. We did not have any positive anti-MDA5 patients. The most relevant clinical findings were similar to those seen in previously published reports. Eleven of the twelve patients with anti-TIF1γ positivity had classical dermatomyositis. Three of the twelve anti-TIF1γ patients had cancer during the disease progression. This was two out of four for the anti-NXP2 subgroup and one in four for the anti-SAE subgroup. In two juvenile dermatomyositis cases, typical ulceration was seen in patients with anti-TIF1γ positivity. The frequency of pulmonary fibrosis during the disease progression was 2/12, 1/4 and 1/4 in anti-TIF1γ, anti-NXP2 and anti-SAE, respectively. Other extra-muscular manifestations, such as arthralgia, dysphagia, dysphonia and dyspnoea, were also detectable. The myositis subgroups determined by these myositis-specific autoantibodies differ from each other in their symptoms, prognosis and therapy responsiveness. Their detection is helpful for the preparation of an adequate treatment, but in daily diagnostic methods, these antibodies cannot be detected. By presenting our anti-TIF1γ, anti-NXP2 and anti-SAE cases, we would like to highlight the clinical role of these antibodies.Autoimmunity Reviews. 01/2014;
Acta Derm Venereol 91
Letters to the Editor 2010 Epub ahead of print
© 2011 The Authors. doi: 10.2340/00015555-0955
Journal Compilation © 2011 Acta Dermato-Venereologica. ISSN 0001-5555
Dermatomyositis (DM) is a systemic inflammatory
myopathy with characteristic cutaneous manifestations
(a heliotrope rash, Gottron’s papules, paronychial ery-
thema and nailfold bleeding) and is often associated with
interstitial lung disease and internal malignancy. Thus
far, some autoantibodies specific for myositis have been
discovered, including antibodies to aminoacyl-tRNA
synthetases (ARS), anti-Mi-2 antibodies, anti-CADM
140 antibody, anti-p155/140 antibody and others (1–3).
The various autoantibody-positive subgroups of DM
vary in their clinical features. Of these myositis-specific
autoantibodies, the anti-p155/140 antibody is a 155-kDa
reactive nuclear protein relevant to cancer-associated DM
(1, 4–8). However, the frequency of malignancies in pa-
tients with anti-p155/140 antibody is undefined because
no large epidemiological studies have been undertaken.
We describe here a patient with anti-p155/140 antibody-
positive DM who had a poorly differentiated metastatic
adenocarcinoma; however, the primary tumour could not
be identified despite comprehensive examination.
A 57-year-old man presented with refractory erythema on the
hands and face, muscle weakness and dysphagia. Two months
before consultation, he had had erythema on the face, which
had spread to the precordium and limbs.
At the first presentation the patient had a typical heliotrope
rash, Gottron’s papules, paronychial erythema, nailfold bleeding
and hyperkeratotic erythema over the elbow (Fig. 1). Blood
examination revealed a high erythrocyte sedimentation rate (62
mm/h), high levels of lactate dehydrogenase (LDH) (295 IU/l),
C-reactive protein (CRP) (8.13 mg/dl), creatine kinase (CK)
(863 IU/l; reference values: 50–200 IU/l), myoglobin (240 ng/
ml) and aldolase (8.6 U/l). The antinuclear antibody titre was
positive at 1:40 with a homogeneous and speckled pattern. As
for tumour markers, carcinoembryonic antigen (CEA) was high
at 115 ng/ml (reference values: < 5.0 ng/ml). He was later found
to be positive for anti-p155/140 antibody by an immunopreci-
pitation study performed using extracts of the leukaemia cell
line, K562 (4, 9) (Fig. 2). Chest computerized tomography (CT)
revealed aspiration pneumonia. However, there were no signs
of interstitial pneumonia.
Biopsy specimens were obtained from the left deltoid muscle
and the Gottron’s papule on the fifth metacarpophalangeal joint
of the left hand. Histology of the muscle showed inflammatory
infiltration of mainly lymphocytes around the muscle fibres. The
muscle fibres showed necrotic changes, including size irregulari-
ties and reduced staining. The skin biopsy showed hyperkeratosis,
thickening of the granular layer, slight lymphocyte infiltration and
pigment incontinence at the dermo-epidermal junction.
On the basis of the clinical and pathological findings, we diag-
nosed this case as DM. Taking into account the high CEA, upper
gastrointestinal endoscopy and colonoscopy, hepatic and mam-
mary ultrasonography, systemic contrast-enhanced CT, head
magnetic resonance imaging (MRI) and tumour scintigraphy
were performed; however, no malignancies were found.
From initial consultation we started the patient on 60 mg/day
of prednisolone and antibiotics for aspiration pneumonia. Since
the cutaneous manifestations and muscle weakness improved,
we gradually tapered the dose of prednisolone. Although these
symptoms did not recur, CEA continued to rise. The systemic
PET-CT scan showed abnormal accumulation of fluorine 18
fluorodeoxyglucose (FDG) in the lymph node swelling in the
supraclavicular fossa and mediastinum. Therefore, a mediastinal
lymph node biopsy was carried out by fine needle aspiration
through upper gastrointestinal endoscopy. On haematoxylin
and eosin staining, the biopsy showed a poorly differentiated
adenocarcinoma. Immunostaining for cytokeratin 7 and thyroid
Anti-p155/140 Antibody-positive Dermatomyositis with Metastases Origina ting from an Unknown Site
Masafumi Ohashi1, En Shu1, Masataka Tokuzumi1, Kei Fujioka2, Tatsuo Ishizuka2, Akira Hara3, Manabu Fujimoto4, Kenzo Kaji4
and Mariko Seishima1*
Departments of 1Dermatology, 2General Internal Medicine, and 3Tumor Pathology, Gifu University Graduate School of Medicine, Yanagido 1-1 Gifu, and
4Department of Dermatology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan. *E-mail: email@example.com
Accepted May 25, 2010.
Fig. 1. (a) Heliotrope rash and (b) Gottron’s papules, paronychial erythema,
and nailfold bleeding were observed on examination.
Fig. 2. Results of immunoprecipitation study: the sera of Cases 1–5 immuno-
precipitated 155-kDa and 140-kDa bands. See Table I for description of cases.
Letters to the Editor
tissue factor-1 (TTF-1) was positive, but immunostaining for
cytokeratin 20 was negative. Taking these histological findings
into account, we suspected that the primary tumour in our pa-
tient was a lung or thyroid carcinoma. Therefore, cervical MRI
and bronchoscopy were performed, but failed to show any signs
of malignancy in these organs.
One month after the mediastinal lymph node biopsy, bone
scintigraphy showed multiple metastases to the ribs. The
patient died of a relapse of aspiration pneumonia 2 days after
re-hospitalization. Autopsy was not carried out due to non-
consent of his family.
Anti-p155/140 antibody is an antinuclear antibody
that appears in a speckled pattern, and its target is
proposed to be transcriptional intermediary factor
1-gamma (10). This autoantibody is strongly relevant
to cancer-associated DM (1, 4) and has a high specifi-
city (95.9%) (6). Cancer onset is mostly concomitant
with DM or occurs within a year of diagnosis of DM
(6). Currently, only the anti-Jo-1 antibody is examined
in routine tests concerning DM. Thus, it is necessary
to develop a simpler and more widely available test
to help precise and early diagnosis of anti-p155/140
The clinical features of anti-p155/140 antibody-posi-
tive myositis are considered to be typical skin eruptions
(such as V-sign rash, heliotrope rash and Gottron’s
papules) and the absence of interstitial pneumonia (1).
Moreover, flagellate erythema is the most significant
type of skin eruption, and most patients have muscle
weakness or elevated serum CK levels (4).
Although flagellate erythema was absent in our patient,
the other typical symptoms and absence of interstitial
pneumonia were all evident, which along with the con-
tinuous increase in CEA levels strongly suggested an
internal malignancy. Indeed, we discovered mediastinal
lymph node metastases and diagnosed their histological
type, but could not identify the primary tumour. The as-
sociation with anti-p155/140 antibody is reported to be
with carcinomas of the stomach, lung, breast and gall
bladder (4). The possible primary cancer in our patient
was thought to be of the lung, but the diagnosis remains
unknown because autopsy was not performed.
In Table I, we have summarized five cases of derma-
tomyositis positive for the anti-p155/140 antibody (Fig.
2), including the present case, reported in our affiliated
hospitals. Although the heliotrope rash was not present in
two cases, none of the cases had interstitial pneumonia.
All except the one patient who could not be examined had
malignant tumours. Four patients with elevated CK levels
showed muscle weakness, and the anti-nuclear antibody
titres were not very high in any of the cases.
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Table I. Characteristics of five cases of dermatomyositis with the anti-p155/140 antibody and no interstitial pnemonia
Poorly differentiated adenocarcinoma (the primary unidentified)
Lung (large cell carcinoma)
Lung (large cell carcinoma)
Metastatic hepatocarcinoma (the primary unidentified)
40× (Hom, Spe)
160× (Hom, Spe)
80× (Hom, Spe)
80× (Hom, Spe)
aReference values of creatine kinase: 50–200 IU/l. bPresent case.
Hom: homogeneous type; Spe: speckled typ.
Acta Derm Venereol 91