Polymyositis / Dermatomyositis

01Definition and overview

The idiopathic inflammatory myopathies (myositis) are a group of rare autoimmune diseases in which the immune system attacks skeletal muscle and often the skin, lungs, joints and heart. The classical division into polymyositis (muscle only) and dermatomyositis (muscle and skin) has been replaced by subgroups defined by the clinical picture, the myositis-specific antibodies and the muscle biopsy:

Many patients once labelled polymyositis turned out, when looked at again, to have inclusion body myositis, necrotising myopathy, the antisynthetase syndrome or a muscular dystrophy. A diagnosis of polymyositis should prompt a second look at the biopsy and the antibodies.

02Etiology and pathophysiology

The cause is unknown. Genes confer risk, above all HLA-DRB103:01, part of the HLA-B8/DR3 haplotype, for most subgroups, and HLA-DRB111:01 for anti-HMGCR myopathy. Triggers proposed or proven include ultraviolet light (dermatomyositis, anti-Mi-2), smoking (anti-Jo-1 with lung disease), viral infections, statins (anti-HMGCR), cancer and immune checkpoint inhibitors.

Each subgroup injures muscle in its own way:

• Dermatomyositis is a disease of small vessels and interferon. Type I interferon is strongly switched on, complement is deposited on capillaries, capillaries are lost and the fibres at the edge of each fascicle, furthest from the blood supply, shrink: perifascicular atrophy. Inflammation sits around vessels and in the perimysium, with B cells and CD4 T cells.
• Polymyositis and inclusion body myositis show cytotoxic CD8 T cells invading muscle fibres that express MHC class I. In inclusion body myositis there is also degeneration: rimmed vacuoles, protein aggregates and mitochondrial changes, which may be why immunosuppression fails.
• In necrotising myopathy, antibodies against SRP or HMG-CoA reductase with complement kill fibres directly, so there is necrosis and regeneration with little inflammation.
• In the antisynthetase syndrome, antibodies against aminoacyl-tRNA synthetases (Jo-1 is histidyl-tRNA synthetase) go with perifascicular necrosis and with inflammation in the lungs.

The antibodies

Myositis-specific antibodies are found in about 60 per cent of patients, and usually only one at a time. Myositis-associated antibodies (anti-Ro52, anti-PM/Scl, anti-Ku, anti-U1 RNP) are also found in other connective tissue diseases. How they are tested and read is in humoral immunity in rheumatic diseases.

03Clinical features

Muscle

The cardinal feature is proximal muscle weakness, symmetrical, coming on over weeks to months: difficulty climbing stairs, rising from a low chair or the floor, lifting the arms to brush the hair, and lifting the head from the pillow, because the neck flexors are weaker than the extensors. Myalgia occurs, but pain is not the main complaint, and the muscles are not usually tender. Weakness of the pharyngeal and oesophageal muscles causes dysphagia and aspiration, and weakness of the diaphragm and respiratory muscles can cause respiratory failure. Distal weakness, facial weakness or ocular muscle weakness suggest another diagnosis, except for the finger flexors in inclusion body myositis.

Skin in dermatomyositis

• Heliotrope rash: a violet or dusky red rash of the upper eyelids, often with swelling around the eyes.
• Gottron papules: violet or red, scaly papules over the knuckles and finger joints; Gottron sign is the flat form over the knuckles, elbows and knees. Both are highly specific.
• Photosensitive erythema of the face, the V of the neck (V sign), the upper back and shoulders (shawl sign) and the outer thighs (holster sign), often itchy, which helps tell it from lupus.
• Nailfold changes: red periungual skin, ragged cuticles and dilated capillaries; a scaly, itchy scalp.
• Calcinosis, especially in juvenile dermatomyositis, and skin ulcers, especially with anti-MDA5.

Mechanic's hands, cracked, thickened skin along the sides of the fingers and the palms, are the sign of the antisynthetase syndrome.

Lungs, heart and joints

• Interstitial lung disease affects up to about half of patients, most with antisynthetase or anti-MDA5 antibodies. It is usually a nonspecific interstitial pneumonia or organising pneumonia pattern; with anti-MDA5 it can progress over weeks to respiratory failure. It decides the prognosis more than the muscle does.
• The heart: myocarditis, conduction defects, arrhythmias and heart failure, often silent; a cause of death.
• Arthralgia and a non-erosive arthritis (most common in the antisynthetase syndrome), Raynaud's, fever and weight loss.

Cancer

Dermatomyositis carries about three times the expected risk of cancer, and polymyositis a smaller rise. The risk is highest from about three years before to three years after the onset of myositis, and the cancers are those common for the patient's age and sex, with an excess of ovarian, lung, pancreatic, gastric and colorectal cancer and non-Hodgkin lymphoma, and breast cancer common among women; nasopharyngeal cancer is the most common in South-East Asia. The myositis can improve when the cancer is treated, a paraneoplastic course.

Inclusion body myositis

Inclusion body myositis creeps on over years after 50: falls because the knees buckle (quadriceps), a weak grip (deep finger flexors) and dysphagia in more than half. The weakness is often asymmetrical, the wrist and finger flexors are weaker than the shoulder abductors, and the CK is normal or only moderately raised.

04Diagnosis and management

Tests

1. 1

   Muscle enzymes

   The creatine kinase (CK) is raised in most patients, up to 50 times normal, and highest in necrotising myopathy; it can be normal in dermatomyositis, especially amyopathic. Aldolase, LDH, AST and ALT also come from muscle, so raised transaminases are not taken for liver disease. Troponin I is the cardiac-specific troponin; troponin T can be raised by damaged skeletal muscle.
2. 2

   Antibodies

   ANA (often positive; Jo-1 gives a cytoplasmic pattern and can be missed), the myositis-specific and myositis-associated antibodies by line blot or immunoprecipitation, and the antibodies of overlap diseases.
3. 3

   Imaging and electrophysiology

   MRI of the thighs with fat-suppressed (STIR) images shows oedema in inflamed muscle, its pattern, and the best place for a biopsy. EMG shows spontaneous fibrillation potentials at rest and short, small, polyphasic motor unit potentials, and excludes neuropathy and myasthenia.
4. 4

   Biopsy

   A muscle biopsy, open or by needle, from a muscle MRI shows to be affected: perifascicular atrophy and perivascular inflammation in dermatomyositis, CD8 T cells invading MHC class I-positive fibres in polymyositis, necrosis with little inflammation in necrotising myopathy, rimmed vacuoles and inclusions in inclusion body myositis. A skin biopsy in dermatomyositis shows an interface dermatitis like lupus. A typical rash with a specific antibody can make a muscle biopsy unnecessary.
5. 5

   Organ screening

   Full lung function with DLCO and HRCT for every patient; ECG, troponin, echocardiography and cardiac MRI if the heart is suspected; a swallowing assessment; and cancer screening.

Classification

The 2017 EULAR/ACR classification criteria give each finding a weight: age at onset, symmetrical proximal weakness, neck flexors weaker than extensors, the heliotrope rash, Gottron papules and Gottron sign, dysphagia, anti-Jo-1 antibodies, raised muscle enzymes and, when a biopsy is done, its findings. Anti-Jo-1, the heliotrope rash, Gottron sign and rimmed vacuoles score highest. A total of 5.5 or more (6.7 with a biopsy), a probability of at least 55 per cent, classifies probable myositis; 7.5 or more (8.7 with a biopsy), a probability of at least 90 per cent, definite myositis. A classification tree then sorts patients into juvenile dermatomyositis, dermatomyositis, amyopathic dermatomyositis, inclusion body myositis and polymyositis. The criteria count only one antibody and do not separate necrotising myopathy or the antisynthetase syndrome, which have their own definitions.

The differential diagnosis of proximal weakness includes hypothyroidism, drugs (a statin's toxic myopathy, steroids, colchicine, alcohol), Cushing syndrome, low potassium, muscular dystrophies, metabolic myopathies, myasthenia gravis, motor neurone disease and viral myositis. Myositis caused by immune checkpoint inhibitors often comes with myocarditis and myasthenia and can be fatal. Polymyalgia rheumatica causes stiffness and pain, not weakness, with a normal CK.

Cancer screening

International guidance stratifies adults by their cancer risk:

Basic screening is a full history and examination, blood count, liver tests, ESR and CRP, serum protein electrophoresis with free light chains, urinalysis and a chest X-ray, on top of national screening programmes. Enhanced screening adds CT of the neck, chest, abdomen and pelvis, cervical screening, mammography, PSA, CA-125 with pelvic or transvaginal ultrasound, and a faecal occult blood test.

Treatment

Treatment aims to restore strength and function, control the skin and protect the lungs. It is shared by rheumatologists, neurologists, dermatologists and chest physicians, with physiotherapy, speech and swallowing therapy.

Intravenous immunoglobulin is the first treatment licensed for dermatomyositis on the strength of a large randomised trial (a small controlled trial had suggested benefit in the 1990s): in the placebo-controlled trial it improved 79 per cent of patients at 16 weeks against 44 per cent on placebo. One 10 per cent product is licensed in Europe for adults with active dermatomyositis treated with immunosuppressants, or unable to take them, and in the United States for adult dermatomyositis. Its risks include thrombosis, kidney injury and headache. In the rituximab trial, most patients with refractory myositis improved, although the trial missed its primary endpoint (giving rituximab early or 8 weeks later made no difference to the time to improvement); antibody-positive patients respond best.

Long courses of steroids bring their own harm, including steroid myopathy, which is suspected when weakness worsens while the CK falls. Patients on high doses need bone protection, co-trimoxazole against pneumocystis pneumonia when they are combined with other immunosuppressants, and checks of glucose and blood pressure. Exercise is safe and helpful once the disease is controlled, and supervised training is started early.

05Epidemiology

The inflammatory myopathies are rare: incidence estimates range from about 2 to 10 or more per million a year, depending on how cases are defined. Dermatomyositis and the antisynthetase syndrome affect women about twice as often as men; dermatomyositis has two peaks, in children aged about 5 to 10 and in adults aged 40 to 60. Juvenile dermatomyositis is the commonest childhood myositis. Inclusion body myositis is the commonest acquired myopathy after 50 and is commoner in men. Anti-MDA5 disease and its lung disease are more frequent in East Asia. Anti-HMGCR myopathy is rare, a few cases per 100,000 people taking statins, but common statin use makes it an important diagnosis.

06Prognosis

With early treatment most patients with dermatomyositis, the antisynthetase syndrome and necrotising myopathy regain much of their strength, though many need years of immunosuppression and relapses are common when it is reduced. Some are left with weakness, contractures, calcinosis or the effects of long steroid courses.

The outlook is set by the organs beyond muscle. Mortality is two to three times that of the general population, and the main causes of death are cancer, interstitial lung disease, infection and heart disease. Older age, cancer, dysphagia, heart involvement and lung disease worsen the prognosis; rapidly progressive lung disease with anti-MDA5 antibodies has killed up to about half of patients within months in some series, although survivors often stay in remission. Anti-Mi-2 dermatomyositis has a good prognosis, and anti-SRP myopathy is often severe. Inclusion body myositis shortens life little, but disability grows steadily: many patients need a walking aid within 10 to 15 years. Follow-up checks strength, the CK, swallowing, lung function and, for three years after diagnosis, cancer.