Long-term outcome in polymyositis and dermatomyositis.

BACKGROUND: Although polymyositis and dermatomyositis are regarded as treatable disorders, prognosis is not well known, as in the literature long-term outcome and prognostic factors vary widely. AIM: To analyse the prognostic outcome factors in polymyositis and adult dermatomyositis. METHODS: We determined mortality, clinical outcome (muscle strength, disability, persistent use of drugs and quality of life) and disease course and analysed prognostic outcome factors. RESULTS: Disease-related death occurred in at least 10% of the patients, mainly because of associated cancer and pulmonary complications. Re-examination of 110 patients after a median follow-up of 5 years showed that 20% remained in remission and were off drugs, whereas 80% had a polycyclic or chronic continuous course. The cumulative risk of incident connective tissue disorder in patients with myositis was significantly increased. 65% of the patients had normal strength at follow-up, 34% had no or slight disability, and 16% had normal physical sickness impact profile scores. Muscle weakness was associated with higher age (odds ratio (OR) 3.6; 95% confidence interval (CI) 1.3 to 10.3). Disability was associated with male sex (OR 3.1; 95% CI 1.2 to 7.9). 41% of the patients with a favourable clinical outcome were still using drugs. Jo-1 antibodies predicted the persistent use of drugs (OR 4.4, 95% CI 1.3 to 15.0). CONCLUSIONS: Dermatomyositis and polymyositis are serious diseases with a disease-related mortality of at least 10%. In the long term, myositis has a major effect on perceived disability and quality of life, despite the regained muscle strength.

Polymyositis: an overdiagnosed entity.

BACKGROUND: According to widely used criteria (Bohan and Peter criteria, 1975), dermatomyositis (DM) is differentiated from polymyositis (PM) only by skin changes. More recent criteria also include histopathologic characteristics enabling the distinction between PM and DM and the differentiation of sporadic inclusion body myositis (s-IBM) from PM. The authors investigated the applicability of diagnostic features for diagnosing PM and DM. METHODS: The authors performed a retrospective follow-up study of 165 patients with 1) a previous diagnosis of myositis; 2) subacute onset of symmetric, proximal weakness; and 3) an evaluation between 1977 and 1998 excluding other neuromuscular disorders. RESULTS: The diagnoses at initial evaluation based on clinical, laboratory, and histopathologic criteria were PM, 9 (5%); DM, 59 (36%; 54 isolated, 3 with associated connective tissue disease [CTD], 2 with associated malignancy); unspecified myositis (perimysial/perivascular infiltrates, no PM or DM), 65 (39%; 38 isolated myositis, 26 with associated CTD, 1 with malignancy); and possible myositis (necrotizing myopathy, no inflammatory infiltrates), 32 (19%; 29 isolated myositis, 3 with associated CTD). At follow-up evaluation, five of the nine patients with PM had typical s-IBM features. None of the remaining four patients complied with the assumed typical signs of PM. Ten of the 38 patients with isolated unspecified myositis had been diagnosed with a CTD. CONCLUSIONS: Polymyositis is an overdiagnosed entity. At evaluation, more than half the patients with autoimmune myositis cannot be specifically diagnosed with polymyositis or dermatomyositis. A quarter of patients with isolated unspecified myositis subsequently developed connective tissue disease.

Necrotising myopathy, an unusual presentation of a steroid-responsive myopathy.

OBJECTIVE: To evaluate the clinical features, muscle pathology and response to treatment in patients with a necrotising myopathy, without mononuclear cell infiltrates. BACKGROUND: Mononuclear cell infiltrates in the muscle biopsy specimen are the diagnostic hallmark of the immune-mediated idiopathic inflammatory myopathies (IIM). In patients with the typical clinical features of IIM, absence of these infiltrates in the muscle biopsy specimen casts doubt on the diagnosis and leads to uncertainty about therapeutical strategies. METHODS: A detailed description is given of the clinical, laboratory, and histopathological features of eight patients suspected of having an idiopathic inflammatory myopathy, in whom mononuclear cell infiltrates in their muscle biopsy specimens were lacking. RESULTS: Eight patients (five men, three women, age range 40-69 years) had severe, symmetrical proximal weakness with a subacute onset. There were no skin abnormalities suggesting dermatomyositis. Serum creatine kinase activity was more than 10 times elevated. Repeated muscle biopsy specimens, taken from a symptomatic muscle prior to immunosuppressive treatment showed widespread necrosis, regeneration, and atrophy of muscle fibres, but no mononuclear cell infiltrates. Known causes of necrotising myopathy were excluded. Three patients had a malignancy. Adequately dosed and sustained immunosuppressive treatment eventually resulted in normal or near normal muscle strength in seven patients. One patient showed marked improvement. CONCLUSION: Occasionally, patients who clinically present as an idiopathic inflammatory myopathy may lack mononuclear cell infiltrates in their muscle biopsy specimens. This subacute-onset progressive necrotising myopathy should not deter the clinician from timely and appropriate treatment as we consider this myopathy to be steroid-responsive with a possible immune-mediated pathogenesis.

Evidence for heterogeneity of T cell expansion in polymyositis and inclusion body myositis.

Vbeta usage of muscle-infiltrating T lymphocytes in polymyositis (PM) and sporadic inclusion body myositis (s-IBM) was correlated with clinical and histopathological features. Immunohistochemical analysis was combined with complementarity-determining region 3 (CDR3) length analysis in nine muscle biopsies of eight PM patients and six biopsies of five s-IBM patients. Vbeta usage was heterogeneous in seven patients. Four of these patients had definite PM with endomysial located T cell infiltrates, but T cells specifically surrounding and invading individual non-necrotic fibers were not found. In two s-IBM patients, Vbeta 2 usage was increased. In one of them, a repeat biopsy showed a heterogeneous Vbeta usage. We conclude that clonal expansion of muscle-infiltrating T cells could only be detected in part of the patients. Explanations may be that clonal expansion does not take place in all disease phases and that PM is a heterogeneous disease with respect to pathogenesis.

[Three patients with divergent presentations of idiopathic inflammatory myopathy]. / Drie patiënten met uiteenlopende presntaties van idiopathische inflammatoire myopathie.

The group of idiopathic inflammatory myopathies encompasses polymyositis, dermatomyositis and inclusion body myositis. These diseases share the following features: progressive muscle weakness, an increase in serum creatine kinase activity and the presence of mononuclear cell infiltrates in the muscle biopsy. Polymyositis, dermatomyositis and inclusion body myositis are differentiated on the basis of the distribution of muscle weakness, and specific histopathological features. Many specialties may see these patients as the clinical presentation can vary widely and may be atypical, requiring further diagnostic procedures. A 40-year-old man with a heliotrope rash and periorbital oedema, but no muscle involvement, was diagnosed with dermatomyositis sine myositis. He was successfully treated with corticosteroids but died later of cardiac failure. A 72-year-old man with a pulmonary malignancy subsequently developed the clinical features of dermatomyositis. Steroid therapy diminished the complaints but he died of pulmonary embolism. A 54-year-old woman with the clinical features of inclusion body myositis did not have rimmed vacuoles in her muscle biopsy specimen and was initially erroneously diagnosed with polymyositis, for which she was treated with corticosteroids, but without beneficial effect.

Rimmed vacuoles and the added value of SMI-31 staining in diagnosing sporadic inclusion body myositis.

Problems in diagnosing sporadic inclusion body myositis may arise if all clinical features fit a diagnosis of polymyositis, but the muscle biopsy shows some rimmed vacuoles. Recently, immunohistochemistry with an antibody directed against phosphorylated neurofilament (SMI-31) has been advocated as a diagnostic test for sporadic inclusion body myositis. The aims of the present study were to define a quantitative criterion to differentiate sporadic inclusion body myositis from polymyositis based on the detection of rimmed vacuoles in the haematoxylin-eosin staining and to evaluate the additional diagnostic value of the SMI-31 staining. Based on clinical criteria and creatine kinase levels in patients with endomysial infiltrates, 18 patients complied with the diagnosis of sporadic inclusion body myositis, and 17 with the diagnosis of polymyositis. A blinded observer counted the abnormal fibres in haematoxylin-eosin-stained sections and in SMI-31-stained sections. The optimal cut-off in the haematoxylin-eosin test was 0.3% vacuolated fibres. Adding the SMI-31 staining significantly increased the positive predictive value from 87 to 100%, but increased the negative predictive value only to small extent. We conclude that (1) patients with clinical and laboratory features of polymyositis, including response to treatment, may show rimmed vacuoles in their muscle biopsy and that (2) adding the SMI-31 stain can be helpful in differentiating patients who respond to treatment from patients who do not.

[Brain tumor or stroke?]. / Hersentumor of beroerte?

Sometimes, the clinical presentation of a brain tumour mimics that of stroke or vice versa, as exemplified in the following three patients. In a 73-year-old patient the initial clinical picture was compatible with a brachial plexus lesion, as the weakness in his right hand appeared to have a traumatic, and not a central nervous system related, cause. When he experienced a focal seizure, the CT scan of the brain revealed a lesion in the motor cortex. This was presumed to be an infarction due to the lack of mass effect and the absence of contrast enhancement. Shortly afterwards the patient deteriorated and a follow-up scan revealed a large contrast-enhancing lesion. During surgery this proved to be a glioblastoma multiforme. A 76-year-old man was suffering from a progressive neurological deficit. An MRI scan of the brain revealed a contrast-enhancing lesion and a chest X-ray revealed an asymptomatic lung tumour; the diagnosis 'brain metastasis' was made. The surgeon removed the lung tumour, which proved to be a carcinoma. Later, when the patient was referred to the neurosurgeon for extirpation of the presumed brain metastasis, the MRI scan revealed that the lesion had decreased in size and no longer exhibited contrast enhancement. The metastasis proved to be an infarction. A 53-year-old man presented with sudden loss of consciousness due to a haemorrhage in the occipital lobe. An angiogram did not reveal a vascular malformation and during surgery no abnormal tissue was seen. The patient almost made a complete recovery. However, several months later he developed an elevated intracranial pressure due to a large occipital high-grade glioma, which had caused the original haemorrhage.

Oral pulsed high-dose dexamethasone for myositis.

To study the short-term effect of oral pulsed high-dose dexamethasone for myositis we treated eight newly diagnosed patients with three 28-day cycles of oral dexamethasone. Primary outcome measures were muscle strength, pain, and serum creatine kinase activity. Six patients responded. Side effects were mild. At follow-up five responders were still in remission, without medication. Pulsed high-dose dexamethasone seems beneficial in myositis. A larger, prednisone-controlled trial is justified to analyze long-term efficacy.

Absence of characteristic features in two patients with inclusion body myositis.

According to recently published criteria a diagnosis of definite sporadic inclusion body myositis is made if the typical histopathological abnormalities (rimmed vacuoles and abnormal accumulations of proteins, in addition to mononuclear cell infiltrates) are present. The two women described here presented with myositis which was unresponsive to treatment. Patient 1 had features of non-progressive sporadic inclusion body myositis clinically, whereas patient 2 had a very slowly progressive limb girdle syndrome. The cryostat sections of the first biopsies did not show rimmed vacuoles, even in retrospect. Only a repeated biopsy, 12 years after presentation in one patient and 18 years after presentation in the other, disclosed the typical features of sporadic inclusion body myositis. The initial absence of abnormal fibres probably represents a real absence or scarcity rather then a sampling error due to a multifocal nature of the histological abnormalities. It is of importance for the clinician to realise that some patients with myositis unresponsive to treatment, even if both clinical and histological features do not suggest sporadic inclusion body myositis, may prove to have the disease on repeated histopathological examination.