doi:10.1093/brain/awv192
BRAIN 2015: 138; 2485–2492
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REPORT
Anti-Jo-1 antibody-positive patients show
a characteristic necrotizing perifascicular
myositis
Lénaig Mescam-Mancini,1,* Yves Allenbach,2,3,* Baptiste Hervier,2,4,* Hervé Devilliers,5
Kuberaka Mariampillay,2 Odile Dubourg,6 Thierry Maisonobe,6 Romain Gherardi,7
Paulette Mezin,1 Corinna Preusse,3 Werner Stenzel3 and Olivier Benveniste2
*These authors contributed equally to this work.
Idiopathic inflammatory myopathies can be classified as polymyositis, dermatomyositis, immune-mediated necrotizing myopathy,
sporadic inclusion body myositis or non-specific myositis. Anti-Jo-1 antibody-positive patients are assigned to either polymyositis
or dermatomyositis suggesting overlapping pathological features. We aimed to determine if anti-Jo-1 antibody-positive myopathy
has a specific morphological phenotype. In a series of 53 muscle biopsies of anti-Jo-1 antibody-positive patients, relevant descriptive criteria defining a characteristic morphological pattern were identified. They were tested in a second series of anti-Jo-1
antibody-positive patients and compared to 63 biopsies from patients suffering from other idiopathic inflammatory myopathies.
In anti-Jo-1 antibody-positive patients, necrotic fibres, which strongly clustered in perifascicular regions, were frequently observed.
Sarcolemmal complement deposition was detected specifically in perifascicular areas. Inflammation was mainly located in the
perimysium and around vessels in 90.6%. Perimysial fragmentation was observed in 90% of cases. Major histocompatibility
complex class I staining was diffusely positive, with a perifascicular reinforcement. Multivariate analysis showed that criteria
defining perifascicular pathology: perifascicular necrosis, atrophy, and perimysial fragmentation allow the distinction of antiJo-1 antibody-positive patients, among patients suffering from other idiopathic inflammatory myopathies. Anti-Jo-1 antibodypositive patients displayed perifascicular necrosis, whereas dermatomyositis patients exhibited perifascicular atrophy.
1 Département de Pathologie, Institut de Pathologie, Centre Hospitalier Universitaire, Grenoble, France
2 Département de Médecine Interne et Immunologie Clinique, Centre de Référence Maladies Neuro-Musculaires Paris Est,
Assistance Public – Hôpitaux de Paris (AP-HP), DHU I2B, Université Pierre et Marie Curie (UPMC), INSERM UMRS 974, Hôpital
Pitié-Salpêtrière, Paris, France
3 Department of Neuropathology, Charité-Universitätsmedizin, Berlin, Germany
4 INSERM: CIMI-Paris, INSERM UMRS-1135, UPMC, Paris
5 Département de Médecine Interne, Hôpital Dijon, Dijon, France
6 Laboratoire de Neuropathologie, Centre de Référence Maladies Neuro-Musculaires Paris Est, AP-HP, Hôpital Pitié-Salpêtrière,
Paris, France
7 Institut Mondor de Recherche Biomédicale INSERM : U955, Université Paris-Est Créteil Val-de-Marne (UPEC), IFR10, 94010
Créteil, France
Correspondence to: Yves Allenbach,
Département de Médecine Interne et Immunologie Clinique,
Centre de Référence des Maladies Neuro-musculaires Paris Est,
Groupe Hospitalier Pitié Salpêtrière,
Assistance Publique Hôpitaux de Paris,
Received December 12, 2014. Revised May 9, 2015. Accepted May 10, 2015. Advance Access publication July 21, 2015
ß The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved.
For Permissions, please email: [email protected]
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L. Mescam-Mancini et al.
83 boulevard de l’Hôpital Paris Cedex 13 France
E-mail: [email protected]
Keywords: anti-synthetase; idiopathic inflammatory myopathies; dermatomyositis; polymyositis; necrotizing myopathies
Abbreviations: ASS = anti-synthetase syndrome; DM = dermatomyositis; IIM = idiopathic inflammatory myopathy;
IMNM = immune mediated necrotizing myopathy; MHC = major histocompatibility complex
Introduction
To date, idiopathic inflammatory myopathies (IIMs) are
classified in five categories: polymyositis, dermatomyositis
(DM), immune-mediated necrotizing myopathy (IMNM),
sporadic inclusion body myositis and non-specific myositis
(Hoogendijk et al., 2004). Pathological analysis of skeletal
muscle biopsies represents an important element for classification of IIM (Hoogendijk et al., 2004). In addition to the
five histological patterns currently associated with the five
main categories of idiopathic inflammatory myopathies,
there are 415 myositis-specific autoantibodies. Some of
these autoantibodies, including anti-tRNA-synthetase autoantibodies, define more homogenous groups of patients
than current histopathological classifications. Similarly,
Love et al. (1991) and later, Koenig et al. (2007) proposed
a clinicoserological classification including a new category:
overlap myositis, for patients harbouring myositis-specific
autoantibodies. The anti-histidyl-tRNA synthetase antibody
(anti-Jo-1) is the most common myositis-specific autoantibody, encountered in 20–30% of patients with IIM
(Brouwer et al., 2001). Anti-aminoacyl-tRNA synthetase
antibody-positive patients suffer from myositis associated
with specific extramuscular manifestations, which include
interstitial lung disease, arthritis, Raynaud’s phenomenon
and mechanic’s hands, defining the relatively homogenous
disease called anti-synthetase syndrome (ASS) (Love et al.,
1991; Brouwer et al., 2001). Whether ASS-associated myositis is an independent disease among IIM or should be
classified among known entities such as polymyositis,
dermatomyositis, IMNM or overlap myositis, is a matter
of debate (Targoff, 2002; Hirakata, 2005; Betteridge et al.,
2007; Koenig et al., 2007). However, this issue is crucial
for understanding pathophysiology and development of
therapies.
The aim of our study was to determine if Jo-1 myopathy
is associated with a specific morphological phenotype, as
the extramuscular manifestations suggest a distinct disease.
Materials and methods
Patients
First, muscle biopsies of 53 Jo-1 patients (French series) were
analysed retroactively. Anti-Jo-1 antibodies had been identified
using two different standard methods (Luminex-100 system;
Luminex, or the ENA-LISA, Biomedical Diagnostics). Clinical
signs of patients and ancillary data were documented by two
of the co-authors (B.H., O.B.) using the same methodology as
described previously (Hervier et al., 2012; Stanciu et al., 2012).
In a second part of the study, muscle biopsy specimens of
19 Jo-1 patients (German series) were analysed. Patients were
identified based on similar diagnostic criteria as those in the
French series.
In addition, the IIM control groups consisted of muscle biopsies from patients tested negative for anti-Jo-1, anti-PL7 and
-PL12 antibodies (n = 63), suffering from dermatomyositis
(n = 20), immune-mediated necrotizing myopathy (IMNM;
n = 21) and sporadic inclusion body myositis (n = 22). All patients fulfilled ENMC criteria of dermatomyositis and IMNM
(Hoogendijk et al., 2004). Sporadic inclusion body myositis
was diagnosed according to the Hilton-Jones criteria
(Benveniste and Hilton-Jones, 2010).
According to the principles of the Declaration of Helsinki,
informed consent was obtained from all patients and the
Charité ethics committee approved the study (EA1/204/11).
All patients gave informed consent to participate in the
study, and approval was obtained from the French institutional review board (AC 2012 1724).
Histological analysis
Seven-micrometre cryostat sections of muscle biopsies were
used for the study. Stains and immunophenotyping of inflammatory cells were performed as previously described (Preusse
et al., 2012; Allenbach et al., 2015), using an automated slide
staining system (BenchMark XT, Ventana Medical Systems).
The term ‘perimysial’ describes alterations in the connective
tissue domain in between the fascicles, and the term ‘perifascicular’ describes alterations in the muscle fibre domain at the
very edge (two penultimate layers) of the muscle fascicles
(Wedderburn et al., 2007).
Double immunofluorescence of utrophin and C5b-9 was performed with the same protocol and repeated with a second
primary antibody and an appropriate secondary antibody.
For vascular assessment, endothelial cells were stained with
utrophin in Jo-1 patients (n = 20), dermatomyositis patients
(n = 19) and compared to patients with normal muscle biopsies
(n = 7).
Electron microscopy
Ultrastructural analysis was performed by the same methodology as described previously (Preusse et al., 2012).
Histological quantifications
First, all slides from the French series were retroactively analysed. Presence or absence of each item is mentioned. Necrosis
Muscle pathology in Jo-1 patients
was defined by pale and/or hyalinized staining by haematoxylin and eosin. Regenerating fibres were identified by increased
basophilia with haematoxylin and eosin staining as well as
large vesicular nuclei and by foetal myosin or NCAM staining.
Additionally, a semiquantitative analysis was performed
for assessment of inflammation, fibre necrosis, and C5b-9
deposition on capillaries: inflammation and necrosis were
scored 0: absent, 1: mild and 2: prominent; C5b-9 capillary
deposits score was 0 if no deposit, 1 if 45; 2 if 6–10, and
3 if 410 capillaries showed deposits. The localization
(perimysial, endomysial or perifascicular) of lymphocytes and
necrosis was recorded. The perifascicular region was defined as
the two penultimate myofibre layers at the periphery of fascicles, and perifascicular necrosis was considered if more than
two-thirds of the total number of necrotic fibres occurred in
perifascicular regions.
The German series of Jo-1 patients and the abovementioned
control groups were analysed blinded to diagnosis.
For vascular assessment, 10 randomly selected areas were
photographed at an original magnification of 200-fold using
the Olympus DP25 camera. For each picture the number of
whole muscle fibre sections and capillaries were manually
counted, and the capillary:fibre ratio was calculated (Estruch
et al., 1992).
Statistical analysis
The Mann-Whitney or the Kruskal-Wallis tests were used to
compare histological characteristics between inflammatory
myopathy groups, when appropriate. A P-value 50.05 was
considered significant.
Features associated with presence of Jo-1 antibodies were
studied, using a model of logistic regression. The parameters
listed in Supplementary Table 1 were used as independent variables in a logistic model with a stepwise backward selection as
well. The diagnostic performance of the score was illustrated
by the receiver operating characteristic curve (SAS 9.3
software).
Results
Characteristics of the patients
Characteristics of Jo-1 patients (French, n = 53) are
reported in Table 1. As expected, all Jo-1 patients presented
a myopathy with at least two of the following features:
proximal weakness, myalgia, myogenic changes on electromyogram and/or high creatine kinase levels. In the second
group of Jo-1 patients (German n = 19), the mean age was
46.7 15.5 years and 60% were female. In the IIM control groups, DM patients were 48.2 18.4 years old,
84.2% female; IMNM patients were 57.6 16.6 years
old, 66.6% females; sporadic inclusion body myositis
patients were 68.6 5.1 years old, and 40% were
female. DM patients were anti-Mi-2 antibody-positive in
27.2% of the cases and IMNM patients were either
anti-signal recognition particle (SRP) (56%) or anti-
BRAIN 2015: 138; 2485–2492
3-hydroxy-3-methyl-glutaryl-CoA
(44%) auto-antibody-positive.
reductase
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(HMGCR)
Perifascicular fibre injury in Jo-1
patients
The most salient feature of Jo-1 patients’ biopsies was presence of necrotic fibres in general (86.8% of patients had
necrotic fibres), which strongly clustered in perifascicular
regions (75.8%) (Fig. 1A). In line with the predominance
of necrotic fibres in perifascicular regions, regenerating
fibres were frequently observed (83%), mainly in the
same area. Immune stainings using anti-CD56, anti-foetal
myosin and anti-utrophin antibodies, confirmed the presence of regenerating fibres in perifascicular areas
(Supplementary Fig. 1). Atrophic myofibres occurred frequently and clustered in perifascicular regions with conspicuous irregular distribution, as 58.8% of patients
harboured this pattern. Sarcolemmal complement deposition was restricted to perifascicular fibres (75%)
(Fig. 1B). Sarcolemmal complement deposition occurs in a
subgroup of regenerating fibres in Jo-1 patients, whereas
we did not observe substantial co-labelling in DM patients
(Supplementary Fig. 1).
Major histocompatibility complex (MHC) class I staining
was diffusely positive in 92.2%, with a perifascicular
reinforcement in 58.8% of cases (Fig. 1C).
Perimysial inflammation in Jo-1
patients
Inflammation was present in 50 biopsies (94.3%): scores
1 and 2 were noted in 43.4% and 51% of cases, respectively. The infiltrate was mainly located in the perimysium
and/or around vessels in 90.6%, with extension into the
endomysium in 83.0% (Fig. 1A). Endomysial lymphocytes
invading (43.4%) or surrounding (60.4%) non-necrotic
fibres were present. Additionally, inflammation was associated with perimysial fragmentation, which was highlighted by alkaline phosphatase staining (90% of cases)
(Fig. 1D), and by ultrastructural analysis illustrating loculation in the perimysial fibrous tissue as well as swollen fibroblasts (Fig. 1E).
CD68 + macrophages were most abundant and detected
in all cases, T cells were found in nearly all cases (CD4 +
cells: 93%; and CD8 + cells 90.5%), while CD20 + B cells
were observed in 62% of the cases.
Topographically, macrophages and CD8 + cells were
found both in the endomysium, and perimysium
(Fig. 1F). CD4 + cells were mainly seen in the perimysium
and around vessels extending into the endomysium in 50%,
whereas CD20 + B cells were nearly exclusively detected in
the perimysium (Fig. 1F).
Together these results showed that Jo-1 patients exhibit
perimysial and perifascicular pathology.
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L. Mescam-Mancini et al.
Table 1 Clinical characteristics of 53 Jo-1 patients
(French series)
the receiver operating
(Supplementary Fig. 2).
characteristic
curve
of
0.91
Patients
Mean age at ASS diagnosis (year) n = 53
Gender (females) n = 53
Muscle involvement
Myalgia n = 45
Muscle weaknessa n = 53
Mean creatine kinase (IU/ml) n = 53
Myogenic syndrome n = 34
Interstitial lung disease n = 53
Polyarthralgia/polyarthritis n = 51
Raynaud’s phenomenon n = 50
Mechanics’ hands n = 50
Other skin lesionsb n = 51
Autoantibodies
Jo-1 n = 53
PL7 or PL12 n = 53
TRIM-21/Ro52 n = 41
Ro60/SSA n = 39
La/SSB n = 39
RNP n = 39
45 14
58.5% (31)
73% (33)
77% (41)
7950 10 460
76% (26)
79% (42)
82% (42)
34% (17)
26% (13)
27% (14)
100% (53)
0% (0)
56% (23)
28% (11)
5% (2)
5% (2)
n = number of patients with available information in the databases; Ab = antibody.
a
Defined as Medical Research Council sum score 44 for at least 51 muscle group
evaluated by manual muscle testing.
b
Including skin rash compatible with a DM rash, sclerodactyly and/or digital ulcers.
Compared to other IIM patients, Jo-1
patients harbour a distinct pattern of
perifascicular injury
Having identified perifascicular necrosis and scattered atrophy to be associated with perimysial inflammation and
fragmentation, we aimed to analyse these items in an independent series of IIM patients to test their specificity,
including Jo-1, DM, IMNM, and sporadic inclusion body
myositis patients.
Eleven relevant descriptive items were analysed
(Supplementary Table 1) defining the perifascicular pattern
of alterations. Univariate analysis showed that items characterizing myositis with perifascicular pathology were
indeed significantly different in Jo-1 patients compared to
those in other IIM patients. These comprised (i) perifascicular necrosis; (ii) perifascicular sarcolemmal C5b-9 deposition; (iii) atrophy and perifascicular atrophy; (iv)
ubiquitous MHC-I staining and MHC-I staining with
increased perifascicular intensity; (v) perimysial inflammation with and without extension into the endomysium; and
(vi) perimysial fragmentation (Supplementary Table 1).
Multivariate analysis identified three items allowing for detection of Jo-1 myositis among IIM. These comprised (i)
perifascicular necrosis; (ii) presence of atrophic fibres; and
(iii) perimysial fragmentation with high odds ratios [32.1
(5.7–181.1), 60.9 (4.2–890.3) and 6.4 (1.2–33.7)], respectively. Combination of these three items gave an area under
Jo-1 patients and their pattern of
perifascicular injury fall into the
category of dermatomyositis
According to ENMC criteria (Hoogendijk et al., 2004),
diagnosis of dermatomyositis was achieved in 77.3% of
cases among our two Jo-1 series. Classical dermatomyositis
was diagnosed in 26.4% of the cases (20.8% ‘definite DM’,
and 5.6% ‘probable DM’), and 50.9% of patients were
diagnosed as possible ‘DM sine dermatitis’, as they did
not harbour skin lesions compatible with dermatomyositis
rash (Table 1). The remaining 22.6% of patients were diagnosed as polymyositis (3.7% as definite and 18.8% as
probable). Of note, all ‘polymyositis patients’ harboured
necrosis, but a diagnosis of IMNM was not made due to
presence of at least one exclusion criterion (such as presence of C5b-9 deposits of fibres or significant inflammatory
infiltrates) (Hoogendijk et al., 2004). Thus, strict application of actual diagnostic criteria mainly led to the diagnosis
of dermatomyositis because the region of injury is similar in
Jo-1 and DM patients.
Dermatomyositis-like vascular
pathology also occurs in Jo-1 patients
To differentiate DM and Jo-1 patients, we asked whether Jo-1
patients also showed signs of vasculopathy commonly
observed in DM (Hoogendijk et al., 2004). Vasculopathy in
Jo-1 patients was evidenced by C5b-9 deposits on capillaries,
rarefaction of capillaries or presence of endothelial tubuloreticular inclusions. Capillaries showed C5b-9 deposits adjacent
to the perimysium in 84% of the Jo-1 cases, but mainly with a
low intensity (score 3, 32%; score 2, 26%; and score 1, 26%,
respectively) (Fig. 2A). Compared to dermatomyositis, this
percentage was not significantly different from the one
observed in patients with dermatomyositis (95%, P = 0.4).
Conspicuous capillaries were observed in both groups, but
more frequently in Jo-1 patients (100% and 84% in DM
and Jo-1 patients, respectively, P = 0.01) (Fig. 2B). A rarefaction of capillaries (Fig. 2C), evidenced by low capillary:fibre
ratio, was observed in Jo-1 patients (1.13 0.23), but the
difference was not significant compared to that in DM patients
(1.03 0.31; P = 0.13). This ratio in patients with normal
muscle biopsy was higher (1.58 0.26) compared to both
Jo-1 and DM patients (P 5 0.001) (Fig. 2D). Furthermore,
ultrastructural analysis revealed tubuloreticular inclusions in
endothelial cells in 47% of Jo-1 patients versus 100% in DM
patients (P = 0.0001) (Fig. 2E). Together, these results show
that vascular changes commonly observed in DM also
occurred in Jo-1, differences were, however, only detectable
using ultrastructural analysis.
Muscle pathology in Jo-1 patients
BRAIN 2015: 138; 2485–2492
A
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B
*
*
*
200 µm
100 µm
D
C
100 µm
200 µm
F
E
100
Percentage
80
60
E
E>P
40
P>E
P
20
0
5 µm
CD68+ CD8+ CD4+ CD20+
cells cells cells cells
Figure 1 Pathological changes in Jo-1 + patients showing perifascicular myofibre necrosis and perimysial inflammation. (A)
Necrosis (black arrows) and regenerating fibres (arrow head) are mainly located in the periphery of the muscle fascicle. Atrophic fibres also
appear in the perifascicular area (white arrow) leading to perifascicular atrophy with irregular size of myofibres. Inflammation occurs in the
perimysium (black asterisk shows an infiltrate near a perimysial vessel) inflammation further extends into the endomysium (white asterisk)
(haematoxylin and eosin staining). (B) C5b-9 decorating myofibres is mainly observed in perifascicular areas (black arrow) as well as on necrotic
fibres with a cytoplasmic C5b-9 stain (arrow head). Perifascicular inflammation is present (black asterisk). (C) Diffuse MHC class I staining,
enhanced in perifascicular regions. (D) Alkaline phosphatase staining illustrating prominent perimysial fragmentation (red granular staining, black
arrow). (E) Electron microscopy illustrates swollen fibroblasts and loculation of the perimysial tissue. (F) Distribution of the different subsets of
mononuclear inflammatory cells in skeletal muscle biopsies of Jo-1 patients. P = presence in the perimysium; E = endomysium;
Jo-1 patients harbour a ‘perifascicular
necrotizing’ myositis and DM patients
harbour a ‘perifascicular atrophy’
myositis
To further investigate whether perifascicular pathology
observed in DM patients differs from that in Jo-1 patients,
we compared the characteristics of the perifascicular pathology in both groups. We selected the following relevant
criteria to define perifascicular pathology: necrotic fibres,
atrophic fibres, sarcolemmal positivity for C5b-9, MHC
class I immunostaining mainly occurring in perifascicular
regions and perimysial fragmentation or perimysial inflammatory infiltrates. Of note, univariate analysis showed that
these criteria were significantly more frequent in Jo-1 and
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L. Mescam-Mancini et al.
A
B
100 µm
100 µm
D
C
2.5
***
2.0
***
1.5
1.0
0.5
100 µm
0.0
Jo1+
DM
NM
E
Figure 2 Vasculopathy in skeletal muscle biopsies of Jo-1 patients. (A) Pathological C5b-9 deposits on endothelial cells (black arrows).
Of note, physiological C5b-9 staining on small arteries (black arrowheads). (B) Conspicuous capillaries (black arrows) in perifascicular regions
(utrophin staining). (C) Capillary loss delineated by the red line (utrophin staining of endothelia). (D) Capillaries versus fibres ratios in DM
patients (DM), Jo-1 patients (Jo-1) and in patients with a normal biopsied skeletal muscle based on pathological analysis (NM). (E) Tubuloreticular
inclusions in an endothelial cell (electron microscopy) in a Jo-1 patient’s muscle ***P 5 0.001.
DM patients compared to the others IIMs (data not
shown).
Multivariate analysis showed that Jo-1 patients displayed
perifascicular necrosis more frequently (79% versus 35%,
P = 0.007) whereas DM patients exhibited perifascicular atrophy more frequently (85% versus 63%, P = 0.04) (Table 2).
Characteristics of muscle inflammation were not significantly
different between both groups.
Discussion
In this study comprising 72 Jo-1 patients and 63 patients
with other IIMs, we show that Jo-1 patients harbour a very
characteristic ‘necrotizing perifascicular myositis’ whereas
DM is characterized by a ‘perifascicular atrophy myositis’.
Importantly, the region of interest in necrotizing perifascicular myositis is the perifascicular area, a phenomenon that
was first highlighted by Pestronk (2011) who coined the term
of immune myopathy with perifascicular pathology (IMPP)
comprising Jo-1 myopathies, and IMPP patients with skin
involvement are frequently classified as having dermatomyositis (Pestronk, 2011). This may explain why Jo-1 patients
have been classified as DM patients.
However, the extramuscular phenotype of Jo-1 patients is
clearly different from the one in DM patients. In particular,
Muscle pathology in Jo-1 patients
BRAIN 2015: 138; 2485–2492
Table 2 Perifascicular pattern in Jo-1 and DM patients
Pathologic features
DM
(n = 20)
Jo-1
(n = 19)
Myofibre necrosis in
perifascicular regions
Myofibre atrophy in
perifascicular regions
Perimysial fragmentation
Perimysial inflammatory
infiltrates
HLA enhancement in
perifascicular regions
Sarcolemmal positivity for C5b-9
in perifascicular regions
7 (35%)
15 (79%)**
17 (85%)*
12 (63%)
9 (45%)
20 (100%)
14 (74%)
19 (100%)
17 (85%)
15 (79%)
10 (50%)
14 (74%)
*P 5 0.05; **P 5 0.01 calculated after multivariate analysis.
presence of interstitial lung disease in 80% of Jo-1 patients, is present only in a minority of DM cases (Connors
et al., 2010). Furthermore, ‘DM patients’ with interstitial
lung disease frequently encompass an important proportion
of ASS patients (Hamaguchi et al., 2011). In addition, the
characteristic heliotrope rash observed in DM is not a
defining element of ASS, where mechanics’ hands are a
cornerstone. As a result, only 25% of Jo-1 patients in
this series showed skin lesions ‘compatible’ with DM.
Moreover, DM patients generally harbour an increased
risk of malignancy compared to other IIMs and the general
population (András et al., 2008), whereas we and others
have previously reported that this is not the case for Jo-1
patients (Chinoy et al., 2007; Hervier et al., 2012). Of note,
some Jo-1 patients could have also been diagnosed
as having IMNM (Christopher-Stine et al., 2010;
Preusse et al., 2012; Stenzel et al., 2012). However,
necrotic fibres in IMNM are diffusely distributed, and
inflammation per se is less prominent. At variance with
others (Mozaffar et al., 2000), we showed that inflammation and its topography are a conspicuous diagnostic
element.
The characteristic pattern we observed in Jo-1 patients
adds further data to a recent study addressing this topic.
The authors reported that HLA-DR myofibre expression is
more frequently observed in patients suffering from ASS
(82.8%) compared to that in DM patients (27.6%)
(Aouizerate et al., 2014).
To conclude, we observed a uniform and characteristic
myopathological pattern in the largest series of Jo-1 patients to date, which is in line with the well established
homogenous clinical phenotype. This entity shares the
same topography of pathology with DM, which may
have led to previously classifying it as DM. However, it
is the perifascicular necrosis, defining the myopathology
in Jo-1 patients. This implies that Jo-1 patients should no
longer be considered having dermatomyositis or polymyositis, and morphological diagnostic criteria ought to be adjusted accordingly.
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Funding
Société Française de Médecine
Française contre les Myopathies.
Interne,
Association
Supplementary material
Supplementary material is available at Brain online.
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