Laboratory evaluation of the inflammatory myopathies

Abstract

The laboratory plays an important role in the diagnosis, evaluation, and classification of the heterogeneous group of diseases known as the IIM, which are characterized by chronic muscle inflammation. Serial measurements of the levels of muscle-derived enzymes in serum are the traditional laboratory studies used to follow the clinical course of patients with IIM, although other laboratory tests can also be useful in assessing myositis disease activity. Several markers of immune system activation, including cytokines and lymphocyte markers, show promise as possibly more sensitive measures of myositis disease activity. Discovery of a unique group of MSAs over the past decade has provided an immunologic basis for defining relatively homogeneous subsets of patients who share similar clinical features, disease courses, and responses to therapy. Future investigations of novel immunologic activation markers, as well as the cloning and expression of target autoantigens of the MSAs, should allow better diagnostic assays, enhanced prognosis, and a better understanding of the pathogenesis of these disorders.

Damage extent and predictors in adult and juvenile dermatomyositis and polymyositis as determined with the myositis damage index

“…The total MMT score also correlated moderately with the total MDI severity of damage and muscle severity of damage scores in juvenile IIM patients, but not in adult IIM patients. Serum creatinine, a measure of muscle atrophy (18), correlated inversely with muscle severity of damage in both juvenile and adult IIM patients and with total MDI severity of damage in adult IIM patients. Although only some patients had undergone MRI, a T1‐weighted MRI score that averaged muscle atrophy and fatty infiltration correlated moderately with muscle severity of damage in juvenile and adult IIM patients and with total MDI severity of damage in juvenile IIM patients (Table 3).…”

“…The Childhood Health Assessment Questionnaire (C‐HAQ) (16) and the modified Convery Activities of Daily Living (ADL) assessment scale (17) were used to assess functional disability in juvenile and adult IIM patients, respectively. Serum creatinine, a measure of muscle atrophy (18), was adjusted to a common scale, accounting for sex and age differences, using a lower limit of normal of 0.5 mg/dl for children and 0.7 mg/dl for adults. T1‐weighted MR images of the thighs were available for 34 patients with juvenile‐onset disease and 74 patients with adult‐onset disease, and these were read by 1 musculoskeletal radiologist who was blinded to the clinical assessment; muscle atrophy and fatty infiltration were graded on a 0–4 Likert scale and averaged to provide an overall T1‐weighted MRI score (19).…”

The provisional Paediatric Rheumatology International Trials Organisation/American College of Rheumatology/european League Against Rheumatism Disease activity core set for the evaluation of response to therapy in juvenile dermatomyositis: A prospective validation study

“…High levels of enzymes may help to differentiate active disease from disease remission or muscle damage, in which their levels are usually normal or near normal. However, it is well known that many patients have no muscle enzyme elevation at the time of diagnosis (24–28). Furthermore, CK levels and other muscle enzymes often do not correlate with measures of muscle strength, with CK levels improving without a correspondent improvement in muscle function.…”

“…The following preliminary core set measures were assessed at baseline and 6 months later: 1) the physician's global assessment of the patient's overall disease activity on a 10‐cm visual analog scale (VAS) (where 0 = no activity and 10 = maximum activity) (19); 2) muscle strength via the Childhood Myositis Assessment Scale (CMAS) (where 0 = worst and 52 = best) (20–22) and manual muscle testing (MMT) on 8 muscles tested unilaterally (where 0 = worst and 80 = best) (23); 3) serum muscle enzymes (creatine kinase [CK], lactate dehydrogenase, aldolase, aspartate aminotransferase, and alanine aminotransferase) (24–28), whose results were standardized based on the normal values provided by each local laboratory as previously described (14); 4) functional ability via the Childhood Health Assessment Questionnaire (C‐HAQ) (where 0 = best and 3 = worst) (29, 30); 5) the parent's global assessment of the patient's overall well‐being on a 10‐cm VAS (where 0 = very well and 10 = very poor) (19, 29, 30); 6) global assessment of disease activity according to the Disease Activity Score (DAS) (31) and the Myositis Disease Activity Assessment (MDAA) (32). Briefly, the DAS is a 20‐point scale comprising 2 subscales reflecting skin involvement (ranging from 0 to 9) and muscle inflammation (ranging from 0 to 11), with higher scores indicating greater disease activity.…”

Inflammatory myopathies: Issues in diagnosis and management

“…Reparative processes in muscle may be associated with incomplete integrity of muscle membranes, so that the improving patient may show a lag in normalization of serum CK levels. Immature or regenerating muscle fibers express the MB isoform of CK in addition to the usual MM isoform seen in mature skeletal muscle, so the presence of MB may aid interpretation of the laboratory data (24).…”