Inflammatory Muscle Disease treatment
These four cases illustrate some of the complexities and challenges in the management of inflammatory muscle diseases. We have a series of 78 patients, followed at St George's Hospital since diagnosis for up to 28;yr. This series comprises 29 with pure polymyositis, 17 with pure dermatomyositis, 14 with mixed connective tissue disease, seven with malignancies, four with juvenile disease, two with inclusion body myositis, seven with granulomatous myositis and one with focal myositis. At present 40 are in complete remission, of whom 12 are off all treatment. A further 25 are in partial remission, four have resistant progressive disease and nine have died. Further demographic details are shown inIntravenous immunoglobulin treatment
Intravenous Ig is a relatively new and poorly understood treatment, but does seem to have a role in the management of the inflammatory muscle diseases . A beneficial effect of IVIg was first reported in 1993 and subsequently verified in a randomized, doubleblind, placebocontrolled study in dermatomyositis , with evidence of reduced deposition of complement membrane attack complex on capillaries . This has been supported by openlabel observations in adult and childhood polymyositis and dermatomyositis , though the exact mechanism of action remains unknown.
Muscle magnetic resonance imaging
MRI is extremely sensitive to changes in the water content of tissues, and therefore is well placed to assess inflammatory muscle disease where oedema is a pathological hallmark. It is essential to employ the correct pulse sequences for the detection of muscle changes on MRI.Serial muscle MRI is a helpful noninvasive tool both in the initial diagnosis and longterm management of inflammatory muscle disease. Conversely, MRI may demonstrate that persistent weakness and poor muscle bulk is predominantly due to muscle atrophy and fat replacement. This is a common finding in longstanding disease and may be due to damage from the underlying inflammatory disease or steroid myopathy; neither requiring further immunosuppression.
In our series, MR images in persistently weak patients often demonstrate a mixed picture with areas of atrophy and fat replacement and also areas of oedema. In this situation the presence of oedema is important as this indicates that ongoing weakness may at least in part be due to ongoing inflammation that may be attenuated with increased immunosuppression. The images can therefore be very valuable to treatment decisions regarding escalation, change or withdrawal of immunosuppression.
In general it is not possible to differentiate between polymyositis and dermatomyositis with MRI. Both conditions characteristically demonstrate bilateral symmetrical oedema in the muscles of the lower pelvis and thighs . However, there are certain features which may favour a particular diagnosis. In polymyositis, oedema is generally only seen in muscle. In dermatomyositis, oedema may be seen in soft tissues as well as in muscle, and one report has suggested that the rectus femoris and biceps femoris muscles may be relatively spared .
Soft tissue MRI signal intensity of water (oedema) and fat with respect to skeletal muscle
In our unit, at presentation all patients have serum CK and autoantibodies, including Jo1, measured, an EMG, MRI of thighs (or weak area) and a muscle biopsy, which is often guided by the MRI. Occult malignancy is sought with a chest radiogram, mammogram, abdominal ultrasound and serum tumour markers. Muscle strength is assessed with serial reproducible objective measurements using a strain gauge dynamometer, which provides a more sensitive measure of change than the more rigid MRC power scale. The treatment of myositis has recently been reviewed. In our unit firstline treatment for uncomplicated symptomatic polymyositis and dermatomyositis includes oral prednisolone starting with 4060;mg
individual patient basis, usually when azathioprine has been ineffective or poorly tolerated. In cases where the response to this standard induction immunosuppressive regime is poor, we feel it is important to reassess the diagnosis and confirm that there is still active inflammation, possibly repeating the MRI and muscle biopsy before escalating treatment with i.v. Ig and finally intravenous cyclophosphamide. It is especially important not to miss inclusion body myositis (by performing electron microscopy of muscle biopsy) and lateonset dystrophies, which are both currently untreatable and, as such, these patients should be spared toxic therapies. Patients with occult malignancy may also fail to respond well to initial treatment and a review or repeat of the investigations aimed at detecting tumours at the time of diagnosis should be undertaken.
In fulminant or life threatening disease, we use pulses of i.v. methylprednisolone, i.v. Ig or cyclophosphamide early because of their fast mode of action (e.g. cases 1 and 3). In general we favour i.v. Ig over cyclophosphamide because it is less toxic, and we use i.v. Ig as the drug of choice for dysphagia. Intensive monitoring of respiratory function including blood gases on air and early transfer to ITU saves lives. Myoglobinuria is a feature of acute fulminating muscle disease with very high serum CK levels, and urine should be tested in such cases early at presentation (see case 3). Cases with myoglobinuria are medical emergencies where close monitoring of renal function and prompt and intensive treatment is necessary to prevent renal failure and ensure a good outcome.