Possible role for tumour necrosis factor inhibitors in the treatment of resistant dermatomyositis and polymyositis: a retrospective study of eight patients.

OBJECTIVE: To understand the use of tumour necrosis factor (TNF)alpha inhibitors in refractory dermatomyositis and polymyositis in an academic centre. METHODS: A retrospective study of eight patients with dermatomyositis or polymyositis refractory to corticosteroids and immunosuppressives who were treated with TNF inhibitors between 1998 and 2004. RESULTS: 8 patients with dermatomyositis or polymyositis who were treated with TNF inhibitors as adjunct treatment were identified. The mean (SD) duration of disease before initiation of TNF inhibitors was 8.5 (4.4) years. The patients failed to respond to treatment with corticosteroids (oral and intravenous); intravenous immunoglobulin and immunosuppressants (methotrexate, azathioprine, mycophenolate mofetil and leflunomide); 4.5 (1.4) immunosuppressants had been used before TNF treatment. Six patients were treated with etanercept alone, one with infliximab and one sequentially with both agents. Of the eight patients, six showed a favourable response with improved motor strength and decreased fatigue after 15.2 (6.5) months. Two of the patients did not respond after 4 (1.4) months and TNF inhibitors were discontinued. Responders showed a 54.4% (27.7%) decrease in serum concentration of creatine kinase, which was grossly abnormal (4463.5 (4036.4) U/l). Non-responders had similar reductions in creatine kinase concentration (56.1% (20.4%)), but their pre-treatment concentrations were in the normal range (118.5 (19.1) U/l). CONCLUSION: Anti-TNF agents may be useful in some patients with refractory dermatomyositis or polymyositis.

The association of malignancy with myositis.

The exact nature of the relation between malignancy and myositis has created continued controversy. Most of the evidence points toward an association between dermatomyositis (DM) with malignancy. The relation with polymyositis is much weaker, if at all present. The first 5 years after DM diagnosis is when the risk is greatest for malignancy. Although types of malignancy seen in DM and polymyositis are similar to those in the general population, ovarian cancer seems to be more common in DM. Most experts recommend that otherwise asymptomatic patients with DM have an age-specific examination for occult malignancy. All suggestive symptoms or clinical clues should be evaluated thoroughly.

Confounding factors in the management of myositis.

Management of myositis is complicated by the lack of a clear understanding of the disease and the lack of clear diagnostic and therapeutic guidelines. These issues are of particular concern since there can be serious side-effects of first-line therapy and, in the case of dermatomyositis, an associated risk of cancer.

A brief educational intervention for patients with rheumatic disease chosen to be presented in a clinic conference.

Being presented in a case conference can be anxiety-provoking and intimidating for the patient. We observed that patients, at times, would show signs of apparent discomfort. A structured interview of the patient was designed to assess, address, and clarify concerns the patient might have beforehand. The patients' concerns were communicated to the staff. The structured interview was given to 31 patients before they were presented. An additional 14 patients were interviewed after the conference about their experience without the prior interview. One year later, we followed up by interviewing another 15 patients who had been selected for clinic conference cases. The structured interview revealed confusion on the patient's part about the purpose of the conference, and a desire for information about the physical setting and who would be there. Patients wanted to be introduced formally when entering the room and to be thanked when leaving, and preferred to be questioned directly about their symptoms. Of the 31 patients interviewed before the conference, 23 (74%) reported that the conference was a positive experience when questioned afterward, compared with only 9 of 14 (64%) of those who were not interviewed before the conference. The results of this study were presented to the clinic staff, and education of the patients was stressed as a primary responsibility. At the follow up, 12 of the 15 patients reported real understanding of the clinic conference purpose. The only patient who reported being uncomfortable with the clinic conference and unwilling to attend another was the only patient who reported not being informed about what the conference entailed. It can be too easy for medical staff to forget that what is routine to them is very unusual and can be very stressful to the patient.

Strength in polymyositis and dermatomyositis: best outcome in patients treated early.

OBJECTIVE: To study the influence of clinical variables on improvement in muscle strength in patients with polymyositis and dermatomyositis. METHODS: We biomechanically examined muscle strength over the course of 2.54 years of 65 patients. RESULTS: Disease duration before therapy was predictive of outcome. Those treated within 6 months or one year of disease onset had better outcomes than those with later treatment. In addition, among those who gained strength, degree of elevation of creatine kinase was correlated with greater gains. CONCLUSION: Early treatment after disease onset increases the chance of a favorable response.

Sensitive rapid detection of myoglobin in serum of patients with myopathy by immunoturbidimetric assay.

OBJECTIVE: To study immunoturbidimetry, a new technique for the quantitative determination of myoglobin in serum. METHODS: Correlation with the standard technique of radioimmunoassay in sera of patients with and without myopathy. RESULTS: Immunoturbidimetry was found to have a close correlation with the radioimmunoassay (RIA) method (r = 0.97, p = < 0.001), although it was slightly less sensitive. Compared to RIA, sensitivity was 87.8% and specificity, 98.6%. The turbidimetric method was performed considerably more rapidly than RIA. Using this method to assess patients with dermatomyositis and polymyositis, a close relationship to clinical findings was noted. However, of 64 samples with myoglobin level greater than 50 ng/ml, there were 3 instances (4.7%) where elevated myoglobin in the presence of normal CK suggested active disease, and there were 9 instances (14.1%) where myoglobin was normal in the presence of elevated CK. Seven of these cases were felt to reflect a lower sensitivity of the turbidimetric method. The other 2 are not explained. Serial measurements of serum myoglobin correlated well with clinical state in the course of 2 patients illustrated. CONCLUSIONS: Assay of serum myoglobin by immunoturbidimetry may provide a rapid and easily performed method without reliance on radiochemicals. It can be useful in clinical assessment of patients with myopathies, although sensitivity is not quite as high as that of RIA.

Effects of rheumatoid factor, antinuclear antibodies and plasma reagin on the serologic assay for Lyme disease.

Rheumatoid factor (RF), antinuclear antibodies (ANA) and the presence of other spirochetal infections have been reported to be the source of false positive serologic tests of Lyme disease. To evaluate this, we studied their effect upon the Lyme assay in use in our clinical laboratory. Of 64 rapid plasma reagin (RPR) test positive sera, 2 had positive Lyme antibody tests, not statistically different than controls. Of 43 RF positive sera, 2 had positive lyme tests, no different than controls, and 1 of 53 ANA containing sera had positive Lyme tests, again, not different from controls. There was no relationship of titer of RPR or ANA with Lyme results, nor of ANA pattern. Sera containing high titer RF, however, had slight interference, producing an increase in equivocal Lyme assay results. From the other point of view, sera that were Lyme test positive had no increased frequency of RPR or RF, but had an increased frequency of ANA. Therefore, neither RPR, RF or ANA were found to markedly interfere with the Lyme assay. However, Lyme antibodies may interfere with the ANA test.

Abnormalities in quadriceps-hamstring strength. Relationships in polymyositis and dermatomyositis.

Muscle strength determined as torque was measured in patients with dermatomyositis and polymyositis. Patients demonstrated weakness in both quadriceps and hamstring muscle groups. The ratio of quadriceps to hamstring torque (Q:H) was 1.93 +/- 0.38 in controls and 1.60 +/- 0.62 in patients. Patients with Q:H ratios that were below this mean were older, weaker, and were treated with greater doses of prednisone. Fifty-six percent of patients studied initially had low Q:H ratios, and 64% of all patients had low Q:H ratios at some time. The Q:H ratio in patients with steroid and thyroid myopathy, however, was not different than controls. It is hypothesized, therefore, that preferential involvement of the quadriceps group characterizes patients with inflammatory muscle disease.

Creatine kinase activity inhibitor in sera from patients with muscle disease.

Sera from patients with muscle disease contain an inhibitor of creatine kinase (CK) which may lead to underestimation of CK activity. The inhibitor was dialyzable, but was not related to previously described low molecular weight inhibitors of CK. In a small group of patients with myositis, the amount of inhibitor present in serum was correlated with the severity of the illness. Our findings suggest that the CK inhibitor may be released into serum from injured muscle.

Cricopharyngeal obstruction in inflammatory myopathy (polymyositis/dermatomyositis). Report of three cases and review of the literature.

Three adults, 2 of whom had polymyositis and 1 with dermatomyositis, developed dysphagia during the course of their illness. Results of esophageal manometry supplemented with esophageal radiography indicated the presence of cricopharyngeal achalasia. Because of the severity of this disorder, which is associated with aspiration of esophageal contents into the airways, surgery to divide the cricopharyngeal musculature was performed in 2 patients, giving complete relief of their symptoms. Prednisone dosage was not increased to treat this condition since it arose not from weakness but from obstruction. A biopsy specimen taken from 1 patient demonstrated inflammatory changes in the obstructing muscle. A review of these 3 patients and 3 previously reported cases indicates that cricopharyngeal obstruction can be a dominant cause of dysphagia in patients with myositis. The recognition of this entity is important in the management of patients with myositis because: it has serious and potentially life-threatening implications; and in certain cases, it can be effectively treated with surgery.

Creatine kinase MB in skeletal muscle and serum of spine-fusion patients.

The low specificity of creatine kinase (CK) MB elevations for myocardial infarction was confirmed by a prospective analysis of paraspinal muscle and postoperative serum levels of CK-MB. Eleven of 30 patients had serum elevations of CK-MB without myocardial infarction. Elevated CK-MB was not specific for myocardial infarction after spine surgery. CK-MB was found in paraspinal muscle of 93% of patients. CK-MB may be a pathologic marker in patients with spinal disease.

ECG abnormalities in polymyositis.

Electrocardiographic abnormalities were found in 25 (32.5%) of 77 patients with polymyositis. Left anterior hemiblock (13.0%) and right bundle-branch block (9.1%) were the most common abnormalities. No association could be found between these defects and clinical activity of polymyositis, severity of duration of disease, or degree of creatine kinase level elevation. Similarly, there was no association with age or the presence of certain clinical conditions such as rash or arthritis. In only two patients, both children, did an ECG abnormality improve with corticosteroid therapy. Three patients with heart block died suddenly. This study points up the need for continual close observation of patients with inflammatory muscle disease, even after apparent remission.

Effect of vitamin D and its metabolites on developing myogenic cultures.

Growth, protein synthesis and expression of creatine kinase (CK) by embryonic chick myogenic cells are inhibited by vitamin D and certain of its metabolites. 25-OH cholecalciferol was most active in concentrations of 10(-5) - 10(-6) M, with cholecalciferol and ergocalciferol less active in that order. Ergosterol had no activity of this sort. Inhibition of CK was most marked on the 4th and 5th day of culture and was due to suppression of the appearance of CK-NM and MB. CK-BB was not affected and CK-MB was more affected than CK-BB. Skin fibroblasts by comparison were slightly stimulated in growth at 10(-6) M and much less affected at 10(-5) M than the myogenic cells. It is suggested that vitamin D has a direct effect upon the muscle cell, to cause a selective diminution in the production of certain polypeptides.