OTHER AUTOIMMUNE DISEASES

Clinical features

Myositis Myositis – typically, idiopathic inflammatory myositis has

an insidious onset. Dermatomyositis in children and types
associated with neoplasia may present more acutely. Patients
Ernest Choy
with inclusion body myositis have often had symptoms for
several years at presentation. Assessment of muscle strength is
an important measure of disease activity.

Causes of myositis

Infectious agents
Myositis (inflammation of skeletal muscles) has many causes Viral
• Influenza A and B
(Figure 1). Many viruses and drugs can induce transient disease.
• Hepatitis B
In contrast, bacterial infection causes pyomyositis with acute
• Coxsackievirus
focal suppuration and abscess formation. This contribution
• Rubella (natural infection and live-attenuated vaccine)
focuses on idiopathic inflammatory myositis characterized • Echovirus
by chronic inflammation of striated muscle (polymyositis) • HIV
sometimes with involvement of the skin (dermatomyositis). Bacterial
Focal nodular myositis, giant cell myositis and eosinophilic • Staphylococcus
myositis are rare conditions with characteristic features on • Streptococcus
muscle biopsy; they are not covered in detail here. • Clostridium
Idiopathic inflammatory myositis is classified as: • Mycobacterium tuberculosis/Mycobacterium leprae
• primary idiopathic polymyositis Parasitic
• Trichinosis
• primary idiopathic dermatomyositis
• Toxoplasmosis
• dermatomyositis/polymyositis associated with neoplasia
Drugs and toxins
• childhood dermatomyositis/polymyositis associated with Cholesterol-lowering agents
vasculitis • Statins
• polymyositis/dermatomyositis associated with autoimmune • Gemfibrozil
disease • Clofibrate
• inclusion body myositis. • Benzafibrate
Drugs for infections
• Rifampicin
Epidemiology • Sulphonamides
Polymyositis and dermatomyositis affect about 60–80/million • Griseofulvin
• Zidovudine
population. They are more common in Afro-Caribbeans. The
• Cytotoxic agents and immunomodulators
female:male ratio is 2.5:1, except in inclusion body myositis, in
• Hydroxyurea
which similar numbers of females and males are affected. • Vincristine
• Ciclosporin
What’s new • Interleukin-2
Toxins
• L-tryptophan
• Myositis-specific autoantibodies including antisignal
• Alcohol
recognition particles, anti-Mi-2 and anti-PM-Scl may be
Others
useful in the diagnosis of myositis
• Cimetidine
• MRI of inflamed muscles shows increased signal intensity on • Colchicine
T2-weighted sequences • D-penicillamine
• Immunoglobulin is effective in corticosteroid-resistant • Phenylbentazone
dermatomyositis • Procainamide
• Propylthiouracil
• Carbimazole
• Growth hormone
• Tretinoin
Focal nodular myositis
Ernest Choy is Consultant Rheumatologist and Senior Lecturer at Eosinophilic myositis
King’s College Hospital, London, UK. He qualified from the University Idiopathic inflammatory myopathies
of Wales College of Medicine, Cardiff, and trained in medicine and • Dermatomyositis
• Polymyositis
rheumatology at Guy’s and King’s College Hospitals. His research
• Inclusion body myositis
interests include clinical trials and immunotherapy in inflammatory
rheumatic diseases.
1

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 OTHER AUTOIMMUNE DISEASES
• The most common presenting complaint in patients with
myositis is proximal muscle weakness, leading to difficulty in
lifting objects overhead, inability to comb or wash the hair and
problems with climbing stairs and rising from chairs.
• Distal muscle weakness and atrophy may be prominent in
inclusion body myositis, in which finger flexor weakness and
foot drop are common.
• In addition to girdle muscles, other striated muscles including
the bulbar and intercostal muscles may also be weak, leading
to hoarseness, dysphonia, difficulty in initiating swallowing,
regurgitation of liquids and dyspnoea.
• Muscle pain is present in one-half of patients.
Cutaneous features – the skin rash of dermatomyositis can
precede myositis or may occur without muscle involvement.
Erythematous or heliotropic rashes characteristically affect
the eyelids (Figure 2), malar areas, ‘V’ areas of the anterior
chest and the upper back. Gottron’s papules are erythematous,
scaly plaques over the knuckles or fingers (Figure 3) that often
extend onto the forearm.
Involvement of other organs – idiopathic inflammatory
myositis can involve other organs. Figure 4 lists extramuscular
features. A major international effort is under way to determine
the optimal means of assessing activity and damage in skeletal
muscles and other involved organs.
Malignancy – myositis may herald underlying malignancy,
notably in men over the age of 45 years. The prevalence of
neoplasia is estimated at 5%. Dermatomyositis is more common
than polymyositis.
Investigations
General – ESR and C-reactive protein are usually raised.
Mild anaemia may also be present.
Muscle enzymes – creatine phosphokinase (CPK), aldolase,
aspartate and alanine transaminases, and lactate dehydrogenase
are enzymes released by damaged muscles. CPK is the most
specific enzyme in polymyositis and dermatomyositis, but may
be normal or minimally elevated in inclusion body myositis.
CPK may also be normal in late-stage disease with severe
atrophy, and rarely in some cases of dermatomyositis. Raised
2 Heliotropic rash over the eyelid.
(© 2002 King’s College Hospital NHS Trust Photography
Department.)
MEDICINE
3 Gottron’s papules over the knuckle.
(© 2002 King’s College Hospital NHS Trust Photography
Department.)
aspartate and alanine transaminases may cause diagnostic
confusion with liver diseases.
Electromyography (EMG) is a sensitive but nonspecific
method of evaluating myositis. Typical findings are spontaneous
fibrillation potentials, complex repetitive discharges, positive
sharp waves at rest and short-duration, low-amplitude, complex
polyphasic potentials on contraction. However, these features
also occur in non-inflammatory myopathies. Because of the focal
nature of myositis, EMG is normal in up to 10% of patients.
Muscle biopsy – only significantly weak muscles should be
biopsied, to reduce the likelihood of obtaining a false-negative
result. Needle biopsy is less invasive than open biopsy but more
prone to sampling error. The presence of chronic inflammatory
cells with muscle necrosis in the perivascular and interstitial
areas surrounding myofibrils is pathognomonic. Perivascular
inflammation is typical of dermatomyositis, whereas interstitial
inflammation is more characteristic of polymyositis. Degener-
ation and necrosis of myofibrils, phagocytosis of necrotic cells
and myofibril regeneration are more common than inflammation.
In long-standing myositis, fibrous connective tissue and/or fat
replaces necrotic myofibres. Muscle biopsy in inclusion body
myositis shows vacuoles with basophilic granules and both
intranuclear and intracytoplasmic tubulofilamentous inclusions.
The inclusions contain various proteins, including amyloid.
Serum autoantibodies – antinuclear antibodies (ANA) are
present in more than 80% of patients with polymyositis or
dermatomyositis. The specificities of these ANA include Ro
(SS-A), U1 (ribonucleoprotein, centromere, mitochondria) and
tRNA synthetases. Some autoantibodies are more specific for
myositis. The most common is anti-Jo-1, which is directed against
histidyl-tRNA synthetase. Patients with these antisynthetase
antibodies often have a combination of myositis and interstitial
lung diseases. Other myositis-specific autoantibodies are
antisignal recognition particle (anti-SRP), anti-Mi-2 and anti-
PM-Scl. The latter is an antinucleolar antibody that identifies a
subset of myositis patients with features of systemic sclerosis.
Other investigations – chest radiography, pulmonary func-
tion tests, ECG and echocardiography should be performed in
patients with extramuscular manifestations. MRI of inflamed
muscles shows increased signal intensity on T 2-weighted
43 © 2002 The Medicine Publishing Company Ltd
 OTHER AUTOIMMUNE DISEASES

are the long-term side-effects and, in some patients, insufficient

Features of idiopathic inflammatory myositis efficacy. Corticosteroid side-effects occur in 40% of patients with
polymyositis and dermatomyositis and lead to disability,
Constitutional particularly in patients with osteonecrosis and osteoporotic
• Fatigue vertebral fractures. Prophylactic treatment for corticosteroid-
• Fever induced osteoporosis (e.g. bisphosphonates) should be given to
• Weight loss all patients.
Joints Immunosuppressive agents (particularly azathioprine,
• Polyarthralgia and/or polyarthritis methotrexate and ciclosporin) are often used in refractory cases
Calcinosis of polymyositis and dermatomyositis, but their use is based on
• Intracutaneous, subcutaneous, fascial and intramuscular clinical experience and case reports rather than evidence from
calcification (most common in children) may lead to joint randomized controlled trials.
contractures Intravenous immunoglobulin is expensive, but a randomized
Lungs controlled trial by Dalakas et al. has shown it to be effective in
• Interstitial alveolitis and fibrosis corticosteroid-refractory dermatomyositis. The dose is 2 g/kg
• Aspiration pneumonia monthly, given in divided doses over 3 days.
• Pleurisy and pleural effusion Other therapies – plasmapheresis, total-body irradiation,
Heart thymectomy and extracorporeal photochemotherapy have been
• Cardiac arrhythmias used for refractory polymyositis and dermatomyositis. Their
• Myocarditis efficacy remains uncertain. Given the lack of evidence on efficacy,
• Pericarditis and, rarely, pericardial tamponade cost and potential for complications, there is little justification
Gastrointestinal tract for use of these treatments, except possibly in patients with the
• Pharyngeal dysphagia with regurgitation of liquid and food severest disease.
• Dysphonia
• Ulceration and haemorrhage secondary to vasculitis
Peripheral vasculature
Prognosis
• Raynaud’s phenomenon The prognosis of dermatomyositis and polymyositis is uncertain.
• Periungual infarction with fissuring of the digital pads without About one-third of patients return to normal function, but up to
ulceration (machinist’s hands) one-third die or are severely incapacitated and the remainder
Kidney suffer significant weakness. Poor prognostic factors include
• Proteinuria greater age, race (Afro-Caribbean), bulbar involvement, delayed
• Nephrotic syndrome treatment and cardiovascular or pulmonary involvement. ‹
• Mesangial proliferative glomerulonephritis 
• Myoglobinuria
FURTHER READING
Choy E H, Isenberg D A. Treatment of Dermatomyositis and
4
Polymyositis. Rheumatology 2002; 41: 7–13.
Dalakas M C. Progress in Inflammatory Myopathies: Good but not
sequences and may help to determine which muscle to biopsy. Good Enough. J Neurol Neurosurg Psychiatry 2001; 70: 569–73.
Other investigations may be needed in patients with features Dalakas M C. Polymyositis, Dermatomyositis, and Inclusion-body
suggestive of associated neoplasia. Myositis. N Engl J Med 1991; 325: 1487–98.
Dalakas M C, Illa I, Dambrosia J M et al. A Controlled Trial of
High-dose Intravenous Immune Globulin Infusions as Treatment for
Differential diagnosis
Dermatomyositis. N Engl J Med 1993; 329: 1993–2000.
The main differential diagnoses of idiopathic inflammatory myo-
sitis are neuromuscular disorders that can cause proximal mus-
cle weakness (e.g. spinal muscular atrophies, amyotrophic lateral
sclerosis, myasthenia gravis, Eaton–Lambert syndrome, muscular
dystrophies). Other causes of proximal muscle weakness in-
clude osteomalacia, adrenal insufficiency, hypophosphataemia,
hypothyroidism and carcinomatous neuromyopathy.

Management
Corticosteroids are the standard treatment for idiopathic in-
flammatory myositis. Different regimens have been advocated,
but most suggest using high-dose prednisolone, 60 mg/day p.o.
initially. The dose should then be tapered to administration daily
or on alternate days. The major disadvantages of corticosteroids
Acknowledgement
The author thanks Dr Claire Fuller, Consultant Dermatologist,
King’s College Hospital, for providing the clinical illustrations used
in this contribution.

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