IDIOPATHIC

INFLAMMATORY
MYOPATHIES
PROF O O ADELOWO MD, FMCP, FWACP, FRCP
Edin, FRCP(Lond), FAMedS, MACR.
 OUTLINE
 INTRODUCTION
 EPIDEMIOLOGY
 CLASSIFICATION
 AETIOLOGY
 PATHOGENESIS
 CLINICAL FEATURES
 INVESTIGATIONS
 DIAGNOSIS
 DIFFERENTIALS
 TREATMENT
 ASSESSMENT TOOLS
 REFERENCES
 INTRODUCTION
 Idiopathic inflammatory myopathies (IIMs) are a group of
rare heterogeneous muscle disorders muscle inflammation
and progressive muscle weakness, which can result in
impaired endurance and disability.

 Adult-onset IIM can be broadly classified into polymyositis

(PM), dermatomyositis (DM), and inclusion body myositis
(IBM) though other subtypes have been described.

 The aetiopathology of IIM remains unknown, but genetic and

environmental factors probably interact to produce disease.

 Morbidity outcomes relate to skeletal muscle damage and to

well-known complications such as cancer-associated myositis
and interstitial lung disease (ILD).
 EPIDEMIOLOGY 1
 The IIMs are rare diseases, with an annual incidence of
2–7 cases per million and peak age of 50-60years.

 The peak incidence of PM in adults is 40–60 years.

 Although PM and DM may start at any age, Juvenile
PM is much rarer than Juvenile DM.

 The incidence of DM has two peaks, at 5–15 years and

45–65 years.

 A higher incidence of PM/DM has been observed in black

compared to white patients with ratios of 5:1 and 3:1
respectively.
 EPIDEMIOLOGY 2
 Annual incidence of IBM is about 1–2 per million and is
more common in male subjects.

 The mean age at onset is slightly higher in IBM than in

PM or DM, and it rarely occurs before the age of 50 years.

 The IIMs are worldwide disorders, but there is a

latitudinal gradient of PM versus DM, with the latter
being more common in latitudes closer to the equator,
while PM is more common in northern latitudes.

 Thus, the DM:PM ratio correlates directly with UV-light

irradiation, suggesting a potential mechanistic link.
EPIDEMIOLOGY – AFRICA & NIGERIA
 20 PM and 50DM reported from Tunisia over 18 yrs

 6 PM and 15 DM reported from Senegal.

 Case series of 14 patients by Adelowo et al. (2013)

 14 patients (13 female, 1 male). Mean age 35yrs

 7 Probable PM, 4 possible PM

 3 Probable DM
 CLASSIFICATION
 Polymyositis

 Dermatomyositis
 Classic DM
 Dermatomyositis sine myositis (amyopathic DM)
 Dermatomyositis sine dermatitis
 Juvenile dermatomyositis

 Inclusion-body myositis
 AETIOLOGY
 The exact aetiology of IIMs are not known but is
thought to be due to interaction of genetic and
environmental factors.

 Genetic
 HLA
 Non-HLA

 Environmental
 Infections, drugs, UV light, Vit D deficiency, smoking
 AETIOLOGY – ENVIRONMENTAL 1
 Some acute and self-limiting forms of myositis have been
reported with Coxsackie, echo and influenza viral
infections, mainly in children, but their role in chronic
myositis is uncertain.

 In adults, infections with the retroviruses HTLV1 and

HIV has shown histologic resemblance to PM. Myositis
has also been shown in those infected with the parasite
Trypanosoma cruzi.

 However, there has been no success in detecting signs of

a preceding or persisting infection in myositis cohorts,
and thus solid evidence is still lacking.
 AETIOLOGY – ENVIRONMENTAL 2
 UV light is an exogenous modifier that can influence the
clinical phenotype in DM and PM with DM more common
close to the equator and PM commoner with northern
latitudes.

 Vitamin D is involved in immune regulation and reduced

levels has been associated with several autoimmune
conditions including myositis though the exact mechanisms
are still unknown.

 In general, drug-induced myopathies can be distinguished

from IIMs by the history of drug use, the absence of
characteristic histopathologic changes in biopsy specimens,
and improvement on stopping the drug.
AETIOLOGY – ENVIRONMENTAL 3
 AETIOLOGY – ENVIRONMENTAL 3
 An association between smoking and anti-Jo-1–positive
myositis in patients with an HLA-DRB1*03 genotype was
recently reported, suggesting a gene-environment interaction.

 Whether smoking is a risk factor for the development of

myositis in general has not yet been investigated.

 Malignancy and DM are strongly associated, but the link is less

clear with PM. The link may result from a paraneoplastic
phenomenon or following persistent inflammation.

 Recently a novel autoantibody, anti–transcriptional

intermediar factor-1γ (TIF-1γ, or anti-p155/140), was reported
to have a sensitivity of 78% and a specificity of 89% for
diagnosing cancer-associated dermatomyositis.
 PATHOGENESIS
– IMMUNE PATHWAYS
 As part of the adaptive immune response, both humoral
and cell-mediated mechanisms are important in the
pathogenesis of IIM.

 Evidence for a humoral response is as follows:

 (1) about 80% of patients with PM/DM possess antibodies;
 (2) B and plasma cell infiltrates are present in muscle
tissue;
 (3) immunoglobulin transcripts are well represented in
muscle tissue.

 The two differing patterns of distribution, location, and type

of lymphocyte subsets in muscle biopsy tissue described
below are suggestive of two differing cell-mediated
immune pathways, which may overlap.
 PATHOGENESIS 2
 Innate immune mechanisms require the presence
of ancillary molecules, e.g. cytokines, chemokines, and
their receptors.

 Proinflammatory cytokines such as interleukin (IL)-

1α, IL-1β, tumour necrosis factor alpha (TNFα), type I
interferons (INF-α and -β), and High-Mobility Group
Box 1 (HMGB1) are evident in PM/DM muscle tissue.

 IL-1α and HMGB1 may be present in muscle fibres in

the absence of inflammatory infiltrates, suggesting a
role in persisting weakness.

 A type I interferon gene signature is observed in

muscle tissue and peripheral blood in PM/DM.
 CLINICAL FEATURES
 Muscle weakness
 Rash

 Arthritis
 GIT involvement

 Pulmonary involvement

 Cardiac involvement

 Malignancy
 CLINICAL FEATURES 1
 Muscle weakness
 In IIM, the pattern of weakness is usually proximal,
bilateral, and symmetrical over a period of weeks or
months.

 An exception is IBM, in which asymmetric distal

weakness and atrophy are as prominent as the
proximal muscle findings

 Myalgia is present in 25% of cases, typically early on

in the disease course.
 CLINICAL FEATURES 2
 Muscle weakness
 Upper limb symptoms include difficulty combing hair or
reaching up for objects above head height.

 Lower limb weakness is suggested by difficulty rising to a

standing position from sitting and difficulty climbing steps
or pavement curbs.

 Weakness in the abdominal musculature may cause

difficulty sitting up from a supine position, and neck
weakness may lead to problems keeping the head held
upright.

 The facial musculature is generally spared. If present an

alternative diagnosis should be considered.
NAIL BED CHANGES & GOTTRON’S PAPULES
V-SIGN & HELIOTROPE RASH
FOREARM RASH & EXTENSIVE CALCINOSIS
 CLINICAL FEATURES 4
 Joint:
 Articular manifestations may occur early in IIM
disease, in a mild, RA-like distribution.

 It is more common in connective tissue disease

(CTD)/overlap patients or those possessing anti-
synthetase antibodies, and may lead to an initial
misdiagnosis of inflammatory arthritis.

 Gastrointestinal involvement
 Pharyngeal weakness may lead to dysphonia and/or
dysphagia and disordered upper oesophageal motility.
Such patients are prone to aspiration pneumonia.
 CLINICAL FEATURES 5
 Pulmonary:
 ILD in the context of IIM (IIM-ILD) may be present in up to 65% of
cases at diagnosis with variable severity. ILD may occur in patients
with Anti-Jo1 as part of the Antisynthetase syndrome.

 The main forms of IIM-ILD are non-specific interstitial pneumonia

(NSIP) and usual interstitial pneumonia (UIP). NSIP is
distinguished by the presence of an inflammatory component, which
is considered amenable toimmunosuppression, and thus associated
with a more favourable prognosis.

 CVS:
 Clinical cardiac manifestations in IIM are uncommonly reported,
but may manifest as subclinical ECG abnormalities.

 Other manifestations include: conduction defects, congestive cardiac

failure, pericarditis, and valvular heart disease. Right-sided heart
failure from ILD is a common cause of death in IIM.
 CLINICAL FEATURES 6
 Antisynthetase syndrome:
 Anti-tRNA synthetase autoantibodies are associated with peculiar
clinical features including myositis, ILD, Raynaud’s phenomenon,
non-erosive symmetrical polyarthritis in small joints, and scaly
skin changes on the hands, called mechanic’s hands.

 These patients may also have fever at onset and during flares of
the disease. Notably, some patients may present only with ILD or
arthritis and myositis occurs later.

 Overlap disease
 Myositis may also be found in association with other CTDs, such as
systemic sclerosis, systemic lupus erythematosus, Sjogren’s
disease, rheumatoid arthritis, and as part of mixed CTD.

 In CTD/overlap disease, muscle involvement is usually less severe,

and higher doses of steroids may not be required.
 CLINICAL FEATURES 7- MALIGNANCY
 Compared with the normal population, patients with IIM have a
higher risk of malignancy, which in DM occurs in about 30% of cases
with a higher occurrence in men and in old age.

 The risk of malignancy appears greatest at the time of DM diagnosis

and during the first year after diagnosis. However, the risk remains
increased for at least 3–5 years, and possibly for as long as 10 years
after DM diagnosis so screening is essential.

 The type of cancers associated with IIM are lung, ovary, breast,
colon and, more rarely, haematological malignancies, such as
lymphoma.

 In some cases the association between DM and malignancies may be

a paraneoplastic phenomenon, and thus if the cancer is successfully
treated, the DM resolves. However, in other cases the development of
myositis is subsequent to the malignancy or, despite treatment of the
underlying cancer, the IIM does not improve.

 For PM and IBM the association with malignancy is less certain

 INVESTIGATIONS - ENZYMES
 Elevated muscle enzymes reflect the presence of injured or
necrotic muscle fibres.

 Serum enzymes used include Creatine Kinase (most

specific), lactate dehydrogenase, aldolase, aspartate
aminotransferase (AST), and alanine aminotransferase
(ALT).

 Liver disease may be erroneously diagnosed and can be

readily excluded by a normal GGT.

 Improvement in muscle strength usually lags behind

normalization of enzymes, and an enzymatic rise may
predict an impending disease flare.
 INVESTIGATIONS– ENZYMES 2
 CK levels are not always increased in patients with myositis, and
for instance, 10–20% have CK levels within normal range when
first tested, particularly patients with DM and IBM.

 However, an increased serum CK level is not specific for myositis,

as it may be raised in many other conditions and temporarily after
muscle injury or physical exercise.

 Furthermore, normal serum CK levels vary in healthy people; men

have higher levels than women and there are ethnic differences
with African-Americans having higher levels than Caucasian
subjects

 A more specific marker for myocardial damage in patients with

myositis is increased serum levels of cardiac isoform troponin I
(cTnI).

 Other cardiac troponin isoforms, troponin C (cTnC) and troponin T

(cTnT), are less specific and are also expressed in adult skeletal
muscle.
 INVESTIGATIONS - ANTIBODIES
 Autoantibodies are detected in about 60% of patients with
myositis and are subdivided into two groups, based on their
diagnostic accuracy:

 Myositis-specific antibodies (MSAs) and Myositis

associated antibodies (MAAs), the latter mostly occurring
in patients with myositis-overlap syndrome but also in
connective tissue diseases without evidence of myositis.

 Anti-aminoacyl tRNA synthetase (anti-ARS) antibodies are

the most prevalent MSAs, found in 25–35% of cases.

 Anti-Jo-1 is the most common among the anti-ARS

antibodies, found in 20–30% of patients with PM and 60–
70% of patients with ILD
 INVESTIGATIONS - EMG
 Electromyography provides an extension of the clinical
examination in IIM and is important for the exclusion of non-
inflammatory myopathies and neurogenic disorders.

 Classical (EMG) findings in IIM consist of:

 (1) early recruitment of low amplitude, short duration and
polyphasic motor unit action potentials;
 (2) spontaneous fibrillations, positive sharp waves, and increased
insertional activity; and
 (3) high-frequency complex repetitive discharges, which all
correlate inversely with muscle strength in IIM patients.

 These changes are not specific for IIM and may also be seen in
dystrophies and metabolic myopathy. EMG has approximately
90% sensitivity for picking up inflammatory myopathy but this
partly depends on the skill of the neurophysiologist.
 INVESTIGATIONS – EMG 2
 A normal EMG does not preclude myositis, as myositis and
also EMG changes may be focal.

 An advantage of EMG, however, is that several muscles

can be examined during the same test session.

 EMG may also be used to guide a muscle biopsy. However,

this requires some precaution as EMG investigations may
affect the muscle biopsy result.

 As myositis is usually symmetrical it is recommended that

EMG is performed on one side of the body and then, if the
EMG findings indicate myopathy, the muscle biopsy can be
carried out in a contralateral muscle.
 INVESTIGATIONS - IMAGING
 Ultrasound (USS) was the first imaging tool used for muscle
evaluation. Affected muscles usually appear to be normal or
have an increased size and have low echogenicity, and raised
perfusion in cases of acute muscular involvement.

 Echogenicity is increased and muscle size and perfusion are

reduced in the chronic stage.

 MRI is a very sensitive non-invasive technique for localizing

muscle oedema in inflammatory myositis.

 MRI allows sequential examination of large volumes of muscle

and identification of focal myositis, and can also be used to
target areas for muscle biopsy.
 INVESTIGATIONS - BIOPSY
 Muscle biopsy: should be guided by imaging (USS or
preferably MRI) and is important for several reasons:
 (1) to confirm inflammatory myopathic changes;
 (2) to distinguish PM from IBM;
 (3) to exclude other myopathies.

 A positive muscle biopsy is required for a definitive

diagnosis of PM. In patients with skin changes
characteristic of DM the role of muscle biopsy in the
diagnosis is questionable.

 A negative muscle biopsy does not exclude myositis, as

inflammatory changes may be focal, and thus easily missed
owing to sampling error.
 INVESTIGATIONS – BIOPSY 2
 The muscle selected for biopsy should preferably be symptomatic
but not atrophic, because atrophic muscles will show non-specific
end-stage fibrosis and fatty tissue.

 In patients with DM the inflammatory infiltrates mainly have a

perivascular and perimysial location and are dominated by CD4 T
cells and macrophages. Occasionally, B cells are found.

 In PM the inflammatory infiltrates are mainly located in the

endomysium surrounding muscle fibres. In these infiltrates there
is a high prevalence of CD8 T cells, but also CD4 T cells and
macrophages.

 Pathologically, IBM is similar to PM. In addition, characteristic

findings are rimmed vacuoles and intracellular amyloid deposits
or 15–18 nm tubofilamentous inclusions found on electron
microscopy.
 INVESTIGATIONS – CANCER SCREEN
 In addition to careful history-taking and examination,
laboratory evaluation should include the following: full
blood count, ESR, routine biochemistry, tumour
markers, chest radiography, urinary cytology, and
chest/abdomen/pelvic CT scans.

 Mammography and gynaecological examination is

justified in female patients, as is testicular examination
in males.

 Faecal occult blood testing and gastroscopy/colonoscopy

should be carried out in all patients over 50 years of age.
DIFFERENTIALS
DIFFERENTIALS
 TREATMENT
 Initial treatment of choice in inflammatory myositis is
with corticosteroids.

 The typical initial dose is 0.75–1 mg/kg (e.g. 60–80 mg

prednisolone) per day for 3–4 weeks, and after
normalization of CK and clinical parameters, dose
reduction by 20–25% every 3–4 weeks until the lowest
dose to control the disease is reached.

 Treatment with intravenous methylprednisolone 1 g

daily for 3 days is usually necessary in aggressive
disease.
 TREATMENT 2
 Methotrexate and azathioprine are the most commonly used
steroid-sparing or 2nd line agents.

 Ciclosporin, tacrolimus, cyclophosphamide, and MMF have also

been used.

 IVIG, Plasma exchange for very difficult cases.

 For DM, Sunscreen is essential. Topical steroids or tacrolimus is

usually effective.

 Exercise and rehabilitation programmes are safe and of benefit in

stable treated myositis patients, improving function and aerobic
fitness.

 Treatment of underlying malignancy in Cancer induced IIM cases

 TREATMENT - IBM
 IBM is usually resistant to treatment with glucocorticoids
and other immunosuppressive agents, although there are
anecdotal reports of patients with IBM who have responded
to various immunosuppressive treatments.

 A diagnosis of IBM should always be considered in

treatment-resistant cases of PM.

 Because of its resistance to treatment with

immunosuppressive drugs it has been questioned whether
IBM is an autoimmune disease or rather a degenerative
muscle disease supported by abnormal accumulation of
proteins, such as amyloid-β, in muscle fibres.