Multimodality imaging and the emerging role of cardiac magnetic resonance in
Sophie Mavrogenia,⁎, Theodoros Dimitroulasb, George D. Kitasc
aOnassis Cardiac Surgery Center, Athens, Greece
bDepartment of Rheumatology, Dudley Group NHS Foundation Trust, Russells Hall Hospital, Dudley, West Midlands, DY1 2HQ, UK
cArthritis Research UK Epidemiology Unit, University of Manchester, Manchester, UK
a b s t r a c ta r t i c l ei n f o
Received 4 May 2012
Accepted 16 May 2012
Available online 19 May 2012
Cardiac magnetic resonance imaging
Autoimmune responses and inflammation are involved in the excess cardiovascular risk observed in patients
with systemic inflammatory diseases. Autoimmune myocarditis is a presentation of an inflammatory reaction
of the heart during the course of autoimmune disorders, with most cases seen in systemic lupus erythematosus.
ing to delayed diagnosis when dilated cardiomyopathy or heart failure has already advanced. Therefore, a major
issue is whether the diagnosis of myocarditis will continue to require invasive procedures such as endo-
myocardial biopsy or can be achieved with non-invasive methods. There is increasing evidence that noninvasive
cardiac imaging, including tissue Doppler echocardiography and cardiac magnetic resonance (CMR), is able to
detect subclinical cases and aid in the initiation of specific treatment when it is more likely to be effective. CMR
T2-weighted (T2-W), early T1-weighted (EGE) images taken after 1 min, and delayed enhanced images (LGE)
taken 15 min after the injection of contrast agent. If 2/3 of the imaging sequences are positive, myocardial
inflammation can be predicted or ruled out with a diagnostic accuracy of 78%. As our understanding of disease
mechanisms improves, multimodality imaging may aid in the development of new diagnostic and therapeutic
strategies for this potentially devastating complication of systemic inflammation, but further studies are needed
to formally evaluate this.
© 2012 Elsevier B.V. All rights reserved.
Myocardial disease in autoimmune disorders
Pathophysiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Clinical presentation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Diagnostic assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Role of imaging in the diagnostic work up of myocarditis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Echocardiography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Nuclear techniques. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
The emerging role of cardiac magnetic resonance imaging (CMR) for the diagnosis of myocarditis
CMR versus endomyocardial biopsy for documentation of myocarditis
Role of CMR in the diagnosis of myocarditis in the course of autoimmune diseases
Therapeutic approaches for autoimmune myocarditis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Conclusion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Take-home messages. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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Autoimmunity Reviews 12 (2012) 305–312
⁎ Corresponding author at: 50 Esperou Street, 175‐61 P. Faliro, Athens, Greece. Tel./fax: +30 210 98 82 797.
E-mail address: email@example.com (S. Mavrogeni).
1568-9972/$ – see front matter © 2012 Elsevier B.V. All rights reserved.
Contents lists available at SciVerse ScienceDirect
journal homepage: www.elsevier.com/locate/autrev
Myocarditis is a rare but potentially fatal form of cardiac disease
characterized by inflammatory cellular infiltration and consequent
myocardial injury, without the blockage of coronary arteries that de-
fine ischemic cardiomyopathy . It is the leading cause of heart
failure in patients under 40 years  and it is considered a precursor
of dilated cardiomyopathy, as 10–20% of affected individuals will de-
velop this complication even in the absence of clinical symptoms .
Myocarditis may be infectious, autoimmune, medication-related or a
result of coexistent conditions. However the physiological distinction
between different subsets of the disease may be difficult, as some ev-
idence supports a transition from a virus-induced myocardial inflam-
matory process to chronic activation of the immune system against
self antigens . The contribution of autoimmunity to the pathophys-
iologyof myocarditisis supported by the geneticlinkagebetweensus-
ceptibility to myocarditis and the major histocompatibility complex
genes , the detection of cardiac-specific autoantibodies [6,7], the
frequent pericardial involvement like pericarditis or pericardial effu-
sion , the association with autoimmune diseases , and the fact
that immunosuppressive treatment is beneficial for some types of
Although accelerated coronary artery disease and ischemic heart
failure have mainly attracted the focus of investigators over the last
two decades, myocarditis directly linked to the inflammatory process
ity and mortality in patients with autoimmune diseases. Most cases are
associated with systemic lupus erythematosus (SLE), with up to 57% of
patients found to have pathologic evidence of myocardial inflammation
in postmortem studies from the 1950s and 1960s , although with
ropsy studies has decreased to about 6–7% [13,14]. Myocarditis due to
autoimmune disorders merits urgent clinical attention because of the
likely progression of the cardiac injury to heart failure or ventricular re-
modeling with potent life-threatening complications . However the
detection of myocardial inflammation is hampered by the nonspecific
pattern of clinical presentation and the lack of specificity of traditional
invasive and non-invasive methods. Endomyocardial biopsy is consid-
eredtobethegold-standard forthediagnosis butit isnot routinelyper-
formed because of the perceived risks and the lack of a widely accepted
inflammation may be focal and in areas not easily accessible, and there-
fore is frequently missed . Recently the introduction of sensitive,
non-invasive cardiac imaging techniques and particularly cardiac mag-
netic resonance imaging (CMR) [17–19] has improved our ability to de-
termine subclinical myocardial inflammation and to identify patients
who could benefit from early targeted therapy.
This review summarises the current state of knowledge regarding
ly focusing on the role of multimodality imaging in the detection, treat-
ment guidance and follow up of patients with autoimmune diseases.
Aspects of pathophysiology of myocardial involvement and treatment
in the context of different rheumatic disease subsets are also discussed.
2. Myocardial disease in autoimmune disorders
The reported frequency of myocardial injury in patients with sys-
temic rheumatic diseases is variable depending on whether clinical
nostic methods applied, the disease setting, the type of studies (cross-
sectional, postmortem autopsy studies etc.), and the initiation or not
of immunosuppressive treatment. It ranges from 100% in Kawasaki dis-
ease and other systemic vasculitides duringtheacute and even the con-
11–50% in rheumatoid arthritis [23,24] and in 10–30% of SLE [16–18].
Unusual causes of myocarditis include – amongst others – cardiac sar-
coidosis , giant cell myocarditis associated with celiac disease ,
thymoma  or other autoimmune disturbances , adult-onset
Still's disease , primary biliary cirrhosis , autoimmune thyroid
disease  and primary Sjogren syndrome  (Table 1).
tis mayoccur concomitantly withotherconditions suchas hypertension,
coronaryarterydisease oratherosclerosis whichare commonin patients
with systemic inflammatory diseases resulting in adverse outcome
and higher rates of cardiovascular morbidity and mortality [33–35].
The exact mechanism of myocardial inflammation varies according to
the pathophysiology of the underlying disease. Important roles have
been shown for autoreactive T cells, various proinflammatory cytokines,
natural killer cells and the complement system [36,37].
For example myocarditis in SLE is primarily an immune-complex-
onstrating fine granular immune complex and complement deposition
Autoimmune diseases complicated by myocarditis.
Systemic lupus erythematosus
Adult onset Still's disease
Autoimmune thyroid disease
Primary biliary cirrhosis
Immune-complex associated myocardial injury
Granulomatous and/or non-specific inflammation
Eosinophilic myocarditis with myocardial fibrosis
T-lymphocytes inflammatory infiltration
Interstitial myocardial fibrosis, non- specific inflammatory infiltration
Cardiac myocytes degeneration, non-specific inflammation, giant cells myocarditis (rare)
Non specific inflammation
Giant cell myocarditis
Giant cell myocarditis, non-specific inflammatory infiltration
Steroids, Immunosuppresivesb, IVIG
Steroids, TNF-alpha inhibitors
Steroids, Immunosuppresivesb, IVIG
IVIG: intravenous immunoglobulin, TNF-alpha: tumor necrosis factor — alpha.
aAutopsy based studies.
S. Mavrogeni et al. / Autoimmunity Reviews 12 (2012) 305–312
thelink betweenautoimmunityandlupus myocarditis, thepathogenet-
ic effects of heart-specific and/or SLE-specific autoantibodies in the
progression of myocardial inflammation remain uncertain. In Churg–
Strauss syndrome, a form of systemic necrotizing vasculitis, heart in-
volvement is characterized not only by eosinophilic infiltration and fi-
brosis, but also by active inflammation that may influence therapeutic
decisions, even when the disease is apparently clinically quiescent
an stenosis has been reported . On the other hand two patterns of
myocardial inflammation in rheumatoid arthritis have been described:
a granulomatous form, morphologically identical to the subcutaneous
rheumatoid nodules that are considered specific for the disease, and a
non-specific form that may be also observed in other conditions .
Last but not least, hydroxychloroquine-induced cardiotoxicity repre-
sents another – rare – cause of cardiomyopathy in this population,
whichshouldbeconsidered. Anti-malarialagents are animportant
therapy for SLE, but they are also used in patients with rheumatoid
ic appearance of myocardial fibrosis with myocyte vacuolisation is typ-
ical and specific for the diagnosis . Interestingly, there is no data to
determine the degree to which viral or opportunistic infections may
account for myocarditis in patients with rheumatic diseases.
4. Clinical presentation
The clinical presentation of autoimmune myocarditis is heteroge-
nous and non-specific. Less than 10% of patients  present with
obvious clinical symptomatology indicating that occult and silent
myocardial involvement is more common. However, manifestations
range from mild dyspnoea or chest pain that subside without specific
therapy, to sudden death, with new onset arrhythmias and complete
heart block, hemodynamic instability and cardiovascular collapse or
an acute myocardial infraction-like syndrome. Unexplained fatigue
and diminished exercise tolerance as a result of low cardiac output,
chest pain due to pericarditis or coronary artery spasm and palpita-
tions may also occur . Myocarditis may also be accompanied by
endocarditis and skeletal myositis.
Physical findings are also nondescript but often include a resting
tachycardia that is disproportionate to the patient's temperature,
the development of gallop rhythms, rubs caused by pericardial irrita-
tion, jugular venous distensions, murmurs related to cardiac remodel-
ing and diminished intensity of the first heart sound .
5. Diagnostic assessment
Despite the paucity of typical clinical signs and symptoms, the di-
agnosis of autoimmune myocarditis depends largely on clinical suspi-
cion because of the lack of definite diagnostic tests and a standardised
process. Biomarkers of cardiac injury are elevated in a minority of pa-
tients and consecutive series of autopsies of fatal myocarditis found
anelevated creatinekinaseonlyin18%of thepatients [45,46]. Troponin
I has high specificity (89%) but limited sensitivity (34%) for the diagno-
sis of myocarditis . The presence of anti-troponin autoantibodies in
the serum may cause a false-negative evaluation of troponin levels and
delay treatment. The role of anti-troponin autoantibodies in humans
remains controversial. Previous studies have demonstrated that anti-
In acute myocarditis, the electrocardiogram may show sinus tachy-
cardia with ST segment and T-wave abnormalities but they are usually
Q waves, AV and conduction defects andvariant early repolarisation, but
the sensitivity of the electrocardiogram in myocarditis is low (47%) .
A chest radiograph may disclose cardiomegaly; inthis case the exclusion
of pericardial effusion is necessary. The pathogenesis of recurrent peri-
carditis is still poorly understood and may be related either to viral
infections or autoimmune and autoinflammatory disorders. The im-
mune system plays a major role in the pathogenesis of the disease,
modulating individual responses and explaining the variable reported
recurrence rate (ranging from 20% to 50% of patients) following an
attack of acute or recurrent pericarditis . Coronary arteriography is
warranted in selective cases to rule out ischemic heart disease or
6. Role of imaging in the diagnostic work up of myocarditis
Over the last few years, novel non-invasive imaging modalities, for
evaluation of heart involvement in rheumatic diseases, have advanced
to routine use, where available, providing an alternative method for
the diagnosis of myocarditis without the risks of biopsy. Tissue Doppler
cyasdiagnostic tests in suspected acute myocarditis andtheinterpreta-
tion in patients with systemic autoimmune disorders.
The main echocardiographic findings suggesting the presence of
myocarditis are left ventricular (LV) regional or global dysfunction and
LV dilatation. In a study with histologically proven myocarditis , LV
dysfunction and asynergic ventricular areas were the most common
findings. Right ventricular dysfunction is an independent predictor of
adverse outcome  defined as death or need for cardiac transplanta-
tion. However, these changes were observed only if an extensive lesion
took place and cannot document the definite diagnosis of myocarditis.
There are only few reports of detecting myocarditis by novel echo-
cardiographic modalities such as tissue Doppler, strain and strain rates
also the agreement of tissue Doppler echocardiography and contrast-
enhanced CMR in the diagnosis and management of myocarditis .
diography as equally useful to cardiovascular magnetic resonance in the
diagnosis of myocarditis [53–55].
8. Nuclear techniques
Gallium imaging application, initially used to detect myocarditis,
was diminished, due to lack of specificity . The application of
Indium-111 monoclonal antimyosin antibody imaging with a sensi-
tivity of 100% and a specificity of 58% [56–61], also had severe limita-
tions including limited availability, radiation exposure and 48-h delay
in obtaining imaging after injection to prevent blood pool effects .
Currently, nuclear techniques are not in use for myocarditis detection.
9. The emerging role of cardiac magnetic resonance imaging
(CMR) for the diagnosis of myocarditis
Recently, CMR has emerged as an important technique in the eval-
uation of cardiovascular disease. CMR contributes to the diagnosis of
myocarditis using three types of images: T2-weighted (T2-W), early
T1-weighted (EGE) images taken after 1 min and delayed enhanced
images (LGE) taken after 15 min of the injection of contrast agent.
T2-W is an indicator of tissue free water content, which is in-
creased in inflammation or necrosis, such as during myocardial infarc-
tion or myocarditis (Fig. 1). However, it is not possible to differentiate
between necrosis and inflammation only by the use of T2-W images.
According to some publications, T2‐W has a high sensitivity and speci-
ficity incomparisontobiopsy[63,64].Inanotherstudy, a STIRsequence
was used and the increase in T2 signal intensity demonstrated a good
S. Mavrogeni et al. / Autoimmunity Reviews 12 (2012) 305–312
accuracy in distinguishing patients with suspected SLE myocarditis
from controls . Other investigators also used T2-weighted se-
quences with good results in the detection of myocarditis  (Fig. 1).
To further enhance the detection of pathology on CMR, images
after early (EGE) and late gadolinium (LGE) injection should be
obtained. Higher levels of early myocardial enhancement after gado-
linium administration are due to increased membrane permeability
or capillary blood flow. Membrane permeability is a major contribu-
tor as inflammation damages cell membranes through both T-cell
perforin and B-cell antibody/complement-mediated processes. How-
ever, EGE depends on the assumption that skeletal muscles exhibit
a “normal” pattern of gadolinium enhancement. This assumption is
not of value, if the inflammatory process involves also the skeletal
of late gadolinium enhancement contrast (LGE). The exact pathophysi-
ology of LGE in myocarditis is still under investigation. However,
there are no convincing data showing that high signal intensity (SI) in
LGE images can be caused by edema. In fact, the extensive edema in
Takotsubo cardiomyopathy (a type of cardiomyopathy triggered by
intense emotional or physical stress, that resembles acute myocardial
infarction, but with no evidence of obstructive coronary artery disease,
characterized by transient systolic dysfunction of the apical and/or mid
LV segment with compensatory hypercontraction of the basal segment
of the LV) typically is not associated with LGE. It is clear, that wherever
there is a severe inflammation (with edema), there is at least some ne-
crosis that leads to high SI in LGE images. The experimental data from
Rehwald et al. clearly show that high SI in LGE images specifically
reflects irreversible injury, whereas edema can come with both, acute
reversible and irreversible injury [67,68]. While LGE imaging therefore
is suitable for imaging the extent of injury, it cannot reflect its acuity.
Edema imaging on the other hand, cannot differentiate reversible
from irreversible injury. However, it can differentiate acute from past
tissue damage. The combination of both allows identification of the ex-
tent, reversibility and acuity of any injury, with its regional distribution
patterns providing insights on the etiology. Fibrosis is distinguished by
bright late enhanced areas dispersed in a “cougar-like pattern” [69,70]
(Fig. 2). However, the main discriminator from ischemic necrosis is
the regional distribution, that could be either focal, but also predomi-
nantlyintramuralor, morefrequently, subepicardial[69,70]. Mahrholdt
et al.  found a pathologic LGE in 83 of 87 patients with healed myo-
carditis. Patients without histopathologic evidence of myocarditis did
not have LGE. Myocardial biopsies, targeted to areas with LGE showed
histologic evidence of myocarditis . The pooled data presented in
and two or more of the three tissue-based criteria (edema, increased
membrane permeability or capillary blood flow and fibrosis assessed by
T2, EGE and LGE, respectively) are positive, myocardial inflammation
can be predicted or ruled out with a diagnostic accuracy of 78%; if only
LGE imaging is performed, the diagnostic accuracy is 68%. These findings
indicate that CMR may not be very sensitive, while being very specific
and therefore is very helpful, when it is positive for inflammation .
Additionally, CMR data should also be validated not only for diagnosis
thatcontrast enhancement4 weeks after onset of symptoms was predic-
tive for the functional and clinical long-term outcome and that relatively
early MRI findings may predict longer-term outcomes [15,73].
More sophisticated techniques able to provide detailed information
about both diffuse edema and fibrosis became available more recently.
For this purpose, quantitative T2 mapping could offer the potential for
quantification of myocardial edema [74,75]. Additionally, the applica-
tion of T1 mapping (myocardial mapping of fibrosis), that has been re-
cently used to identify diffuse fibrosis in heart failure, looks promising
for the detection of diffuse fibrosis in myocarditis .
10. CMR versus endomyocardial biopsy for documentation
Endomyocardial biopsy (EMB) is a widely accepted method for diag-
nosing myocarditis, based upon histopathology, immunohistology and
around 6% and the substantial debate about diagnostic criteria for ana-
sensitivity than standard histopathology for the diagnosis of myocardi-
tis. However, cost, availability, and limited standardization have limited
the widespread use of immunohistology andviral genome analysis .
In patients with persisting symptoms, CMR is the ideal test to non-
invasively identify the subjects with persisting inflammation and select
ences sensitivity, specificity, positive and negative predictive values.
Nevertheless, positive predictive value for LGE of up to 85% indicates
that endomyocardial biopsy should be performed “MR-guided” and LGE
seems to have greater sensitivity than endomyocardial biopsy for the di-
agnosis of myocarditis . Additionally, CMR and EMB have good diag-
nostic performances as single techniques in patients with TnI-positive
acute chest pain in the absence of CAD. The combined application of
CMR and EMB yields a considerable diagnostic synergy by overcoming
some limitations of CMR and EMB as individually applied techniques
. Eventually — as soon as appropriate specific therapies, e.g. against
viruses or autoimmune diseases, are available, these patients could
Fig. 1. T2 STIR LV short axis image showing area of edema (white area) in a patient
with fulminant myocarditis.
Fig. 2. LV vertical long axis with epicardial LGE in the posterior wall (white area) due to
S. Mavrogeni et al. / Autoimmunity Reviews 12 (2012) 305–312
receive appropriate therapy very quickly, with possible improvements
11. Role of CMR in the diagnosis of myocarditis in the course of
Until now, CMR has been successfully used for the evaluation of
myocardial inflammation in different types of vasculitis [79–84],
Kawasaki disease , myositis [22,84,85], SLE [17,64,86,88], and
Takayasu arteritis [37,87–90].
As in infective myocarditis, in autoimmune myocarditis, the T2
images represent tissue free water and depict the acute phase of myo-
skeletal muscles exhibit a “normal” pattern of gadolinium enhance-
ment. However, this assumption is not always true, if the inflammatory
process involves also the skeletal muscles, as in inflammatory myopa-
presence of myocardial inflammation . It is also important to notice
that LGE in Churg–Strauss and/or other vasculitides can present an epi-
cardial, intramyocardial and/or more often a diffuse subendocardial
carditis. Another very important point in autoimmune diseases is that
CMR, although more sensitive than any other technique to detect an
early inflammatory myocardial reaction, it is not able to discriminate
cular coronary vasculitis. However, it can act as a gatekeeper to select
autoimmunepatients withmyocardial involvementeven if thesystem-
ic disease seems to be under control and also to evaluate the result of
treatment in the myocardium [17,18,38]. A recent report describes the
potential of CMR imaging based on myocardial first-pass perfusion im-
aging in the visualization of cardiac manifestations in autoimmune vas-
culitis, which in the heart are typically localized at the level of small
mune vasculitis were investigated in this study. Myocardial first-pass
perfusion imaging was performed using an ECG-gated T1-weighted
late. In both cases, CMR showed findings of subendocardial first-pass
perfusion deficit (FPPD), a phenomenon so far described as microvascu-
lar obstruction (MVO) only in patients with acute cardiac infarction due
to thromboembolic obstruction of small myocardial vessels. The two pa-
tients showed local subendocardial and myocardial hypoenhancement
(characterized by a darker appearance than normal myocardial tissue),
which is the typical morphological stigma of FPPD after a bolus injection
of contrast media. The perfusion deficit, although morphologically very
similar to the well-known phenomenon of MVO in acute cardiac infarc-
tion,wasconceivablycaused by different vasculitis-specific mechanisms
acute cardiac involvement in primary andsecondary vasculitis, this type
of subendocardial involvement is typical of Churg–Strauss and does
not necessarily represent the vasculitis pattern in other autoimmune
diseases like rheumatoid arthritis or granulomatosis with polyangiitis.
ondary vasculitis are needed to clarify the role of each sequence in the
evaluation of vasculitis in different types of autoimmune diseases.
CMR also can reveal myocardial inflammation in SLE [18,65] (Fig. 2)
and Churg–Strauss with subtle clinical symptoms and normal inflam-
matory indexes  (Fig. 3). Additionally, it can offer multiple advan-
tages in the evaluation of heart involvement in vasculitis combining
coronary artery anatomy and viability [20,79,80], because in these dis-
eases different pathologic processes, involving different parts of heart
and/or vessels can coexist in the same patient. In Takayasu arteritis,
CMR gives information both about myocardial inflammation and
subclavian arteries or aorta that are frequently involved during the
course of the disease .
LGE proved more sensitive to detect myocarditis in inflammatory
myopathies than conventional laboratory tests, such as creatine kinase,
Troponin I, CRP, or SR [22,84,85]. LGE was also sensitive to changes,
when myositis patients with myocarditis were treated for 6 months
with corticosteroids and other immunosuppressants [89,90] (Fig. 4).
However, its sensitivity and specificity need further evaluation. In sar-
coidosis, during the acute myocardial inflammation, sarcoid infiltrates
are visible on CMR as intramyocardial, epicardial or endocardial hype-
on both T2-weighted and LGE images. The early initiation of corticoste-
roid therapy can prevent malignant arrhythmias and can improve left
ventricular function. According to some studies, LGE was positive in
26% of patients without clinical evidence of cardiac involvement and
were extending to the adjacent endocardium, epicardium, or both .
Additionally, LGE was more than twice as sensitive for cardiac involve-
ment as currently used consensus criteria.Myocardial damage, detected
by LGE, was associated with future adverse events including cardiac
12. Therapeutic approaches for autoimmune myocarditis
There is no consensus for treating autoimmune myocarditis. The
current strategies are mainly empirical based on clinical experience
rather than randomized trials. Supportive treatment for left ventricular
Fig. 3. Short axis LV with extensive subendocardial LGE (white area) due to fibrosis in a
patient with Churg–Strauss vasculitis.
Fig. 4. Extensive intramyocardial andsubepicardial LGEs (white areas) ininterventricular
septum, inferior and lateral wall of LV in a patient with myositis.
S. Mavrogeni et al. / Autoimmunity Reviews 12 (2012) 305–312
dysfunction including angiotensin-converting-enzyme inhibitors or
angiotensin-receptor blockers, beta blockers and diuretics is commonly
recommended. In acute cases accompanied by systemic illness and
hemodynamic imbalance, immunomodulation therapy should be con-
sidered. High-dose corticosteroids orally (e.g. prednisolone 1 mg/kg/
day) or as intravenous pulses (e.g. methylprednisolone 1000 mg/day),
have been accepted as first line treatment by most authors [95,96].
Favorable response to cyclophosphamide or azathioprine, following as
a steroid sparing agent, has also been reported . The administration
of intravenous immunoglobulin in severely ill patients with lupus myo-
carditis refractory to steroids has shown good clinical outcome with
rapid recovery and resolution of left ventricular abnormalities in small
series of patients [98,99]. It has been suggested that IVIG prevents hu-
moral immunity induced myocyte damage through its anti-idiotypic
properties and diminishes the expression and the synthesis of TNF-
alpha, IL-6 and other proinflammatory cytokines . Optimization
of thetreatmentof theunderlyingdiseaseactivityand coexistingcondi-
tions such as hypertension, ischemic heart disease, anemia and renal
impairment should also be addressed.
Novel treatment approaches and different target agents such as
macrophage migration inhibitory factor may contribute to the better
management of autoimmune myocarditis in the future, providing
that the promising results in experimental studies will be confirmed
in humans .
Although autoimmune myocarditis is an uncommon cardiac com-
plication of rheumatic diseases, the functional and prognostic impli-
cations of the diagnosis are important. As our understanding of the
pathophysiology of autoimmune cardiac involvement progresses,
newer and better treatment regimens have improved the clinical
outcome and the prognosis of this subgroup of patients. Enhanced
clinical scrunity alongside evolving non-invasive techniques have im-
proved our diagnostic accuracy and implementation of effective treat-
ment. In that respect, CMR is a promising imaging technique able to
provide early information and possibly change our therapeutic ap-
proach but requires additional validation for the non-invasive diag-
nosis and prognosis in acute and chronic myocarditis during the
course of autoimmune diseases.
• Myocarditis can be detected during the course of many autoimmune
diseases (SLE, RA, Kawasaki,Vasculitis, autoimmune myopathies etc.)
because it performs tissue characterization and reveals the different
pathophysiologic phenomena taking place during inflammation
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Pulse of methylprednisolone versus intravenous immunoglobulin for demyelinating polyradiculoneuropahy
Pulse of methylprednisolone and also intravenous immunoglobulin (IVIg) for the treatment of chronic inflammatory demyelinating poly-
radiculoneuropahy are very used. However, no study has compared these two therapeutical modalities. In a recent article, Nobile-Orazio
et al. (Lancet Neurol 2012;11:478-9) have performed a double-bind, randomized, placebo controlled trial comparing these two therapies
given monthly at standard posology for 6 months. The authors evaluated 21 patients under methylprednisolone and 24 on the IVIg group.
They observed that more patients using methylprednisolone stopped this therapy than IVIg, even after adjustments. The reasons for discon-
tinuation included lack of efficacy, adverse effects or withdrawal. However, the proportion of side effects did not differ between the two
groups. Interestingly, after treatment discontinuation, IVIg patients worsened and needed further treatment than glucocorticoid group. In
conclusion, in patients with chronic inflammatory demyelinating polyradiculoneuropathy, the use of IVIg for 6 months seems to be related
with less discontinuation due to side effects and inefficacy than methylprednisolone.
S. Mavrogeni et al. / Autoimmunity Reviews 12 (2012) 305–312