Myositis - polymyositis and dermatomyositis

What are polymyositis and dermatomyositis?

Polymyositis and dermatomyositis are connective tissue diseases characterised by inflammation of muscles. Idiopathic inflammatory myopathies are a group of chronic, autoimmune conditions affecting primarily the proximal muscles. The most common types of myositis are dermatomyositis, polymyositis, necrotising autoimmune myopathy and sporadic inclusion body myositis (IBM).¹

Although dermatomyositis affects the skin and muscles, it may also affect other parts of the body such as joints, oesophagus, lungs and heart. Both polymyositis and dermatomyositis have an autoimmune basis.

Viral infection has been implicated in the form of the human retroviruses HIV and human T-cell lymphotropic virus type I (HTLV-I), the simian retroviruses, and Coxsackievirus B.

It is possible to divide the conditions into basic subgroups² :

• Polymyositis.

• Dermatomyositis.

• Necrotising myopathy.

• Overlap myositis.

• Inclusion body myositis.

Myositis epidemiology¹

• Few epidemiological studies have been published.

• One US study showed the incidence and prevalence of dermatomyositis to be 1.4 and 5.8 cases per 100,000 people respectively, with female preponderance and a higher prevalence among older age groups.

• For polymyositis, the incidence was 3.8 and the prevalence 9.7 per 100,000 people. However, polymyositis may have been over-diagnosed because not all studies were based on diagnostic muscle biopsies..

Polymyositis^{1 3 4}

History

• There is an inflammatory myopathy with onset over weeks or months and steady progression.

• Diffuse weakness in the proximal muscles develops.

• Proximal myopathy causes difficulty rising from a low chair, climbing stairs , lifting objects and combing hair. Fatigue, myalgia and muscle cramps may also be present.

• Distal muscles are spared, and so fine motor movements of the hand, such as buttoning a shirt, writing, operating a keyboard or playing the piano, are affected only late in the disease.

• Pharyngeal weakness causes dysphagia.

• Weakness may vary from week to week or month to month.

• Only a third have pain. There is no skin rash.

• There is no family history of neuromuscular disease, evidence of endocrine disorder or history of exposure to possible toxins.

Examination

Polymyositis produces muscle weakness. It is not painful, although a few patients complain of aches or cramps.

• Proximal muscle weakness occurs with comparative sparing of distal muscles until the disease is well advanced.

• External ocular muscles are unaffected. Facial muscles are affected only in severe disease.

• Forced flexion of the neck is weak and there may be difficulty just holding the head up.

• Muscular atrophy occurs with preservation of tendon reflexes, flexor plantar response and normal sensation.

• Muscles may be tender on palpation and may have a nodular grainy feel.

Investigations

• Creatine kinase can be up to 50 times normal. It is rarely normal in active disease and the level is usually a good indicator of disease activity.

• About 20% have anti-Jo-1 antibodies. They indicate a poor prognosis with interstitial lung disease, which occurs in about a third⁵ .

• Other enzymes to be elevated include aldolase, serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic-pyruvic transaminase (SGPT) and lactate dehydrogenase (LDH). If SGOT is higher than SGPT, a myogenic cause should be suspected.

• The diagnosis is established by electromyography (EMG) and is confirmed by muscle biopsy. In polymyositis it is the definitive test.

• Cancer antigen 125 (CA 125) and cancer antigen 19-9 (CA 19-9) may be useful markers of the risk of malignancy.

• Autoantibody testing for myositis-specific antibody (MSA) and myositis-associated autoantibodies (MAA) may be useful to differentiate the patients with underlying malignancy⁶ .

Differential diagnosis

Polymyositis is a diagnosis of exclusion and other considerations include:

• Hereditary neuromuscular diseases.

• Endocrine disease including thyrotoxicosis and Cushing's disease.

• Malabsorption syndromes, alcoholism, cancer, vasculitis, granulomatous disease, sarcoidosis or exposure to drugs or toxins that affect the muscles.

Dermatomyositis^{1 3 4}

History

Dermatomyositis affects children as well as adults. The muscle weakness has the same pattern as in polymyositis but there are other features too:

• Rash: see under 'Examination', below.

• There is systemic upset with fever, arthralgia, malaise and weight loss. It can resemble scleroderma with Raynaud's phenomenon and dysphagia.

• Possible cardiac disease including atrioventricular conduction defects, tachyarrhythmias and dilated cardiomyopathy.

• Gastrointestinal ulcers and infections.

• Thoracic muscles may be weak but there may also be interstitial lung disease in 30-50%.⁷

• Children tend to have more non-muscular features, especially gastrointestinal ulcers and infections.

Examination

• The rash includes blue-purple discolouration on the upper eyelids with periorbital oedema, a flat red rash involving the face and upper trunk and raised purple-red scaly patches over the extensor surfaces of joints and fingers. Ulcerative vasculitis and calcinosis of subcutaneous tissue may occur.

• The rash may affect knees, shoulders, back and upper chest and may be exacerbated by sunlight.

• Skin lesions may produce scaling, pigmentation or depigmentation of the skin and a shiny appearance.

• Dilated capillary loops at the fingernail base are typical of dermatomyositis. The cuticles may be irregular and thickened and the palmar and lateral surfaces of the fingers may become rough and cracked.

• Muscle weakness is proximal and can vary from mild to extreme. Sensation is preserved and tendon reflexes are normal unless atrophy is severe.

• There is muscle pain and tenderness early in the disease.

Investigations

• Elevation of creatine kinase is not so reliable although it can be extremely high.

• SGOT, SGPT, LDH, and aldolase levels may also be raised.

• Autoantibodies:
  

  • A positive antinuclear antibody (ANA) finding is common in patients with dermatomyositis.

  • Anti-Mi-2 antibodies are specific for dermatomyositis but found in only 25% of patients with dermatomyositis.

  • Anti-Jo-1 antibodies are more common in patients with polymyositis than in patients with dermatomyositis. They are associated with interstitial lung disease, Raynaud's phenomenon and arthritis.

• MRI is not very helpful for making the diagnosis but it can help monitor activity and guide the best place for muscle biopsy.

• EMG may be helpful but can be normal in 15%. It can also guide a suitable place for biopsy.

• Muscle biopsy can be diagnostic.

Differential diagnosis

Dermatomyositis is much easier to diagnose, as the rash and subcutaneous calcification are typical.

• In systemic lupus erythematosus (SLE), the skin over the phalanges is involved and the skin over the metacarpophalangeal joints is spared. In dermatomyositis, the reverse is true.

• There can be some overlap with systemic sclerosis, rheumatoid arthritis and Sjögren's syndrome but the weakness is more than can be accounted for by arthritis alone.

Associated diseases

• Polymyositis and dermatomyositis may be associated with other autoimmune diseases such as myasthenia gravis, Hashimoto's thyroiditis, systemic sclerosis and Waldenström's macroglobulinaemia.

• Myositis is associated with an increased risk of malignancy, particularly within three years of initial diagnosis. Dermatomyositis appears to have the strongest association with malignancy. Adenocarcinoma has been reported as the most common type of associated malignancy. Certain cancers - eg, ovarian, lung, breast and pancreatic cancer - are particularly increased with dermatomyositis, and lymphatic and haematopoietic malignancies, such as non-Hodgkin's disease, in people with polymyositis.⁸

Polymyositis and dermatomyositis treatment^{9 10}

Non-drug

• Sun-blocking agents should be used.¹¹

• Encourage physical activity within reason to maintain muscular strength. This may involve consultation with a physiotherapist and occupational therapist.

• Evaluation of swallowing may be required and a speech and language therapist may help with difficulties of swallowing.

• Monitor creatine kinase and clinical response but treatment can improve the former without benefiting the latter.

Drugs

Although immunosuppressive and immunomodulatory therapies are frequently used, the optimal therapeutic regimen remains unclear. There is a lack of high-quality studies that assess the efficacy and toxicity of immunosuppressants in inflammatory myositis.¹²

• Early initiation of therapy is essential¹³ .

• Steroids are the most important drugs. In mild disease, topical steroids may suffice. In more severe disease, high doses of systemic steroids are used and tapered off. Improvement is usually apparent by the second or third month. The usual precautions must be exercised when giving high doses of steroids for long periods.

• If steroids fail then immunosuppressive drugs such as azathioprine can be used. As an alternative, cyclophosphamide is usually better than methotrexate.

• Biological agents, including tumour necrosis factor alpha antagonists, intravenous immunoglobulin and rituximab, have been used with varying degrees of success for the treatment of cutaneous dermatomyositis.¹⁴

• Patients with anti-Jo-1 antibodies need long-term immunosuppression.¹⁵

• For lung disease, an aggressive combination regimen including ciclosporin A or tacrolimus with cyclophosphamide is recommended to be added to corticosteroids.⁷

• There have been reviews of treatment options but with few good controlled trials.¹⁶

Complications^{17 18}

• Gastrointestinal ulceration can cause melaena or haematemesis. Infarction of the bowel may occur, especially in dermatomyositis.

• Dermatomyositis can cause subcutaneous calcification that punctures the skin with ulcerations, infection and ugly scars.

• Both dermatomyositis and polymyositis are associated with an increased risk of malignancy.⁸

• Dermatomyositis is also associated with atrioventricular defects, tachyarrhythmias, dilated cardiomyopathies, joint contractures and lung involvement (due to weakness of thoracic muscles, interstitial lung disease).

• Other complications of polymyositis include:
  

  • Interstitial lung disease, aspiration pneumonia.

  • Heart block,arrhythmias, congestive heart failure, pericarditis, myocardial infarction.

  • Dysphagia, malabsorption.

  • Infection.

  • Complications of steroid therapy - eg, osteoporosis, myopathy.

Prognosis¹⁸

• The prognosis of the idiopathic inflammatory myopathies is very variable.

• An associated malignancy indicates a poor prognosis for recovery and increases mortality. Overall, drug-free remissions are rare except in juvenile dermatomyositis.

• Studies have shown that only 20% to 40% of treated patients will achieve polymyositis or dermatomyositis remission, whereas 60% to 80% will experience a polycyclic or chronic continuous course of the disease.

• Mortality remains 2-3 times higher than in the general population, with cancer, lung, cardiac complications and infections being the most common causes of deaths.

• Poor prognostic factors include older age, male gender, non-Caucasian ethnicity, longer symptom duration, cardiac involvement, dysphagia, malignancy and serum myositis-specific antibodies (including co-existence of anti-Ro52 and anti-Jo1 antibodies, presence of antisignal recognition particle antibody, anti-155/140, and anti-CADM-140 antibodies).

• Anti-155/140 antibody is associated with malignancy.