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Objective: The aim of this study was to investigate the feasibility and potential use of quantitative proton magnetic resonance spectroscopy (MRS) for determining metabolite concentrations in patients with suspected inflammatory myopathies., Materials and Methods: In this institutional review board-approved, Health Insurance Portability and Accountability Act-compliant prospective study, 35 patients with a suspected inflammatory myopathy and 6 age-matched healthy volunteers underwent magnetic resonance imaging (MRI) (T1-weighted and short tau inversion recovery [STIR] sequences) and single-voxel MRS (point-resolved spectroscopy; repetition time/echo time, 2000/135 milliseconds; voxel size, 2.0 × 2.0 × 4.0 cm) at 3 T. The voxel was placed in a thigh muscle and targeted to one with abnormal STIR signal when possible. Absolute trimethylamine, creatine (Cr), and bulk lipid concentrations in each voxel were determined using the phantom replacement method. The MRS results of patients and healthy subjects were compared using the Wilcoxon rank sum test., Results: Twenty-one patients were diagnosed with an active idiopathic inflammatory myopathy (IIM). In 20 of these patients, MRI showed increased intramuscular STIR signal; however, the muscle where the voxel was placed was normal in 9 patients. Patients with an IIM demonstrated higher mean intramuscular Cr concentration compared with controls (62.1 vs 35.3 IU; P = 0.01), but there were no differences in the mean trimethylamine or lipid concentrations. In IIM patients with no intravoxel signal abnormality (9/21), the mean Cr concentration was still higher than that in healthy subjects (63.2 vs 35.3 IU; P = 0.001)., Conclusions: Quantitative 3-T MRS is feasible and may supplement the role of conventional MRI in the evaluation of patients with inflammatory myopathies, especially where MRI shows no obvious muscle abnormalities.

Objective: Autoantibodies recognizing 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) are found in patients with statin-associated immune-mediated necrotizing myopathy and, less commonly, in statin-unexposed patients with autoimmune myopathy. The main objective of this study was to define the association of anti-HMGCR antibody levels with disease activity., Methods: Anti-HMGCR levels, creatine kinase (CK) levels, and strength were assessed in anti-HMGCR-positive patients. Associations of antibody level with CK level and strength at visit 1 were analyzed in 55 patients, 40 of whom were exposed to statins. In 12 statin-exposed and 5 statin-unexposed patients with serum from 5 serial visits, the evolution of antibody levels, CK levels, and strength was investigated., Results: Antibody levels were associated with CK levels (P < 0.001), arm strength (P < 0.05), and leg strength (P < 0.05) at visit 1, but these associations were only significant among statin-exposed patients in stratified analyses. With immunosuppressive treatment over 26.2 ± 12.6 months (mean ± SD), antibody levels declined (P < 0.05) and arm abduction strength improved (P < 0.05) in the 17 patients followed up longitudinally. The separate analysis showed that statin-exposed patients developed decreased antibody levels (P < 0.01), decreased CK levels (P < 0.001), improved arm strength (P < 0.05), and improved hip flexion strength (P < 0.05) with treatment. Anti-HMGCR antibody levels did not normalize in any patient., Conclusion: In the entire cohort, initial anti-HMGCR levels correlated with indicators of disease activity; with immunosuppressive treatment, antibody levels declined and arm strength improved. Statin-exposed patients had significant improvements in CK levels and strength whereas statin-unexposed patients did not, suggesting a phenotypic difference between statin-exposed and statin-unexposed anti-HMGCR-positive patients., (Copyright © 2012 by the American College of Rheumatology.)

The inflammatory myopathies are a heterogeneous group of disorders characterized by muscle weakness and inflammation. Although no standard therapeutic guidelines exist, traditional treatment has included corticosteroids and a variety of second-line immunosuppressants. As treatment of refractory disease has been difficult, newer agents and approaches have been used with varying response. The advent of standardized treatment response criteria by the International Myositis Assessment and Clinical Studies (IMACS) group has helped investigators to evaluate and compare clinical trial outcomes in a more rigorous fashion. The use of intravenous immunoglobulin (IVIG), rituximab, biologic agents including tumor necrosis factor (TNF) inhibitors, stem-cell transplantation, gene therapy, and vascular occlusion resistance training are reviewed here. As our understanding of disease pathogenesis at the immunologic, genetic, and molecular level expands, the discovery of novel therapeutic targets hold promise for the successful treatment of these conditions.

Objective: To investigate the association of anti-hydroxymethylglutaryl-coenzyme A reductase (anti-HMGCR) myopathy with HLA class I and II antigens., Methods: HLA antigens were determined in 1) 20 white and 8 African American anti-HMGCR patients, 2) 487 white and 167 African American controls, and 3) 51 white subjects with mild self-limited statin intolerance., Results: White anti-HMGCR patients had a higher frequency of the combination HLA-DR11, DQA5, and DQB7 than controls or statin-intolerant subjects (70% versus 17%; odds ratio [OR] 11.7 [95% confidence interval (95% CI) 4.0-35.3], P = 4.1 × 10(-7) and 70% versus 21%; OR 8.3 [95% CI 2.2-33.9], P = 5.4 × 10(-4) , respectively). This combination was not increased in African American anti-HMGCR subjects compared to controls (13% versus 3%; OR 4.6 [95% CI 0.2-53.3], P = 0.2). However, DR11 was increased in African American anti-HMGCR patients compared to controls (88% versus 21%; OR 26.4 [95% CI 3.1-590.3], P = 0.0002). High-resolution mapping showed that 95% with DR11 had DRB1*11:01. DQA1 and DQB6 were less frequent in white anti-HMGCR-positive patients compared to controls (25% versus 65%; OR 0.2 [95% CI 0.1-0.5], P = 5.5 × 10(-4) and 0% versus 45%; OR 0.0 [95% CI 0.0-0.3], P = 2.1 × 10(-5) , respectively). DRB11 was not associated with particular disease features., Conclusion: DRB1*11:01 is associated with an increased risk of anti-HMGCR myopathy in whites and African Americans. These findings suggest a mechanistic link between statin exposure, increased HMGCR expression, and the possible presentation of HMGCR-derived peptide(s) by DRB1*11:01., (Copyright © 2012 by the American College of Rheumatology.)

Objectives: Elevated serum aldolase A levels occur in the absence of elevated creatine kinase M (CK) levels in a subset of myositis patients. This study was undertaken to investigate the cell biology of this unexplained clinical observation., Methods: Cultured human myoblasts were differentiated in vitro. RNA and protein lysates were prepared and used to determine aldolase and CK gene and protein expression by QPCR and immunoblotting. Cardiotoxin was used to induce muscle injury and repair in an experimental mouse model, and aldolase A and CK were immunoblotted in the muscle lysates. Immunohistochemical staining was performed on myositis patient muscle paraffin sections to assess aldolase A and CK staining in vivo., Results: Aldolase A mRNA and protein expression is highest in differentiating myoblasts, and remains robust throughout differentiation. In contrast, CK mRNA and protein levels are low in undifferentiated myoblasts and become strikingly upregulated as differentiation progresses. Aldolase A protein expression is high in regenerating muscle in the mouse model of injury/repair, while CK expression was low. Immunohistochemical staining of human myositis biopsies showed that muscle cells with the highest levels of aldolase and no CK staining have features of regeneration., Conclusions: In undifferentiated muscle cells, and those early in the differentiation process, aldolase A is expressed in the absence of CK. Thereafter, both are expressed. We propose that isolated serum aldolase A elevation in myositis patients (i) reflects preferential immune-mediated damage of early regenerative cells, and (ii) is a biomarker of damaged early regenerating muscle cells.

Malignant hyperthermia (MH) is a pharmacogenetic, autosomal dominantly inherited disorder of skeletal muscle triggered by volatile anesthetics and infrequently by extreme exertion and heat exposure. MH has variable penetrance with an incidence ranging from 1 in 5000 to 1 in 50,000-100,000 anesthesias. Mutations in the ryanodine receptor gene, RYR1, are found in 50-70% of cases. We hypothesized that a portion of patients with drug-induced muscle diseases, unrelated to anesthesia, such as severe statin myopathy, have underlying genetic liability that may include RYR1 gene mutations. DNA samples were collected from 885 patients in 4 groups: severe statin myopathy (n=197), mild statin myopathy (n=163), statin-tolerant controls (n=133), and non-drug-induced myopathies of unknown etiology characterized by exercise-induced muscle pain and weakness (n=392). Samples were screened for 105 mutations and variants in 26 genes associated with 7 categories of muscle disease including 34 mutations and variants in the RYR1 gene. Disease-causing mutations or variants in RYR1 were present in 3 severe statin myopathy cases, 1 mild statin myopathy case, 8 patients with non-drug-induced myopathy, and none in controls. These results suggest that disease-causing mutations and certain variants in the RYR1 gene may contribute to underlying genetic risk for non-anesthesia-induced myopathies and should be included in genetic susceptibility screening in patients with severe statin myopathy and in patients with non-statin-induced myopathies of unknown etiology., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Idiopathic inflammatory myopathies are a heterogeneous group of autoimmune disorders predominantly affecting skeletal muscles, resulting in muscle inflammation and weakness. The 3 most common inflammatory myopathies are polymyositis (PM), dermatomyositis (DM), and inclusion body myositis. This review details the clinical findings noted in PM, DM, and the emerging entity of autoimmune necrotizing myopathy., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The following article reviews the role of magnetic resonance imaging (MRI) in patients with idiopathic inflammatory myopathies (IIMs), focusing on the 3 major types of IIM: polymyositis, dermatomyositis, and inclusion-body myositis. After a brief introduction with general information about IIM, we will discuss the reasons why MRI plays an important role in the diagnosis and management of patients with polymyositis, dermatomyositis, and inclusion-body myositis. Magnetic resonance imaging can confirm the diagnosis and can help to phenotype the disease. Moreover, the support of MRI is important in addressing the muscle biopsy site and in reducing the high false-negative rate of biopsy when performed in a blind fashion. In monitoring therapy, MRI can add important information about the activity of the muscle disease and can identify cases where continued immunosuppressive therapy is no longer warranted owing to complete fatty replacement of the muscles. Lastly, we provide an overview about some advanced MRI techniques that focus more on function than on morphology of muscle.

Objective: In addition to inducing a self-limited myopathy, statin use is associated with an immune-mediated necrotizing myopathy (IMNM), with autoantibodies that recognize ∼200-kd and ∼100-kd autoantigens. The purpose of this study was to identify these molecules to help clarify the disease mechanism and facilitate diagnosis., Methods: The effect of statin treatment on autoantigen expression was addressed by immunoprecipitation using sera from patients. The identity of the ∼100-kd autoantigen was confirmed by immunoprecipitation of in vitro-translated 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) protein. HMGCR expression in muscle was analyzed by immunofluorescence. A cohort of myopathy patients was screened for anti-HMGCR autoantibodies by enzyme-linked immunosorbent assay and genotyped for the rs4149056 C allele, a predictor of self-limited statin myopathy., Results: Statin exposure induced expression of the ∼200-kd/∼100-kd autoantigens in cultured cells. HMGCR was identified as the ∼100-kd autoantigen. Competition experiments demonstrated no distinct autoantibodies recognizing the ∼200-kd protein. In muscle biopsy tissues from anti-HMGCR-positive patients, HMGCR expression was up-regulated in cells expressing neural cell adhesion molecule, a marker of muscle regeneration. Anti-HMGCR autoantibodies were found in 45 of 750 patients presenting to the Johns Hopkins Myositis Center (6%). Among patients ages 50 years and older, 92.3% had taken statins. The prevalence of the rs4149056 C allele was not increased in patients with anti-HMGCR., Conclusion: Statins up-regulate the expression of HMGCR, the major target of autoantibodies in statin-associated IMNM. Regenerating muscle cells express high levels of HMGCR, which may sustain the immune response even after statins are discontinued. These studies demonstrate a mechanistic link between an environmental trigger and the development of sustained autoimmunity. Detection of anti-HMGCR autoantibodies may facilitate diagnosis and direct therapy., (Copyright © 2011 by the American College of Rheumatology.)

We present the instructive case of a man who developed progressively severe testicular pain. He sought the medical care of several physicians, including general medicine, urology, and rheumatology. What began with focal testicular pain evolved over the ensuing weeks to a multisystem disorder affecting at least 3 additional organ systems beyond the genitourinary tract. Leukocytoclastic vasculitis was diagnosed, affecting the skin, joints, kidney, and gastrointestinal tract with predominant IgA deposition consistent with underlying Henoch-Schönlein purpura in the setting of renal cell carcinoma. This case illustrates and reinforces both the importance of considering an occult malignancy in a patient who presents with symptoms suggestive of a systemic vasculitis as well as the importance of considering an occult vasculitis in the adult male patient presenting with testicular pain.

Objective: The myopathy associated with anti-signal recognition particle (anti-SRP) is a severe necrotizing immune-mediated disease characterized by rapidly progressive proximal muscle weakness, markedly elevated serum creatine kinase (CK) levels, and poor responsiveness to traditional immunosuppressive therapies. Reports on the efficacy of B cell depletion therapy for anti-SRP-associated myopathy are mixed. We describe 8 patients with anti-SRP-associated myopathy and their response to treatment with the anti-CD20 monoclonal antibody rituximab., Methods: We identified 8 patients with myopathy who tested positive for anti-SRP antibodies by immunoprecipitation and were treated with rituximab as part of clinical care. We reviewed their medical records to assess clinical, serologic, and histologic characteristics and response to therapy. In 5 patients, serum was collected before and after rituximab therapy. Autoantibodies were detected by immunoprecipitation and quantitated by densitometry, and the percent decreases in anti-SRP autoantibody levels were calculated., Results: Six of 8 patients who had been refractory to standard immunosuppressive therapy demonstrated improved manual muscle strength and/or decline in CK levels as early as 2 months after rituximab treatment. Three patients sustained the response for 12-18 months after initial dosing. All of the patients were continued on adjunctive corticosteroids, but doses were substantially reduced after rituximab. Quantitative levels of serum anti-SRP antibodies also decreased after rituximab treatment., Conclusion: B cell depletion therapy with rituximab is effective for patients with myopathy associated with anti-SRP. The substantial decrease in anti-SRP antibody levels after rituximab treatment also suggests that B cells and anti-SRP antibodies may play a role in the pathogenesis of this myopathy.

Objective: Myofiber necrosis without prominent inflammation is a nonspecific finding in patients with dystrophies and toxic or immune-mediated myopathies. However, the etiology of a necrotizing myopathy is often obscure, and the question of which patients would benefit from immunosuppression remains unanswered. The aim of this study was to identify novel autoantibodies in patients with necrotizing myopathy., Methods: Muscle biopsy specimens and serum samples were available for 225 patients with myopathy. Antibody specificities were determined by performing immunoprecipitations from (35)S-methionine-labeled HeLa cell lysates. Selected biopsy specimens were stained for membrane attack complex, class I major histocompatibility complex (MHC), and endothelial cell marker CD31., Results: Muscle biopsy specimens from 38 of 225 patients showed predominantly myofiber necrosis. Twelve of these patients had a known autoantibody association with or other etiology for their myopathy. Sixteen of the remaining 26 sera immunoprecipitated 200-kd and 100-kd proteins; this specificity was observed in only 1 of 187 patients without necrotizing myopathy. Patients with the anti-200/100 autoantibody specificity had proximal weakness (100%), high creatine kinase levels (mean maximum 10,333 IU/liter), and an irritable myopathy on electromyography (88%). Sixty-three percent of these patients had been exposed to statins prior to the onset of weakness. All patients responded to immunosuppressive therapy, and many experienced a relapse of weakness when the medication was tapered. Immunohistochemical studies showed membrane attack complex on small blood vessels in 6 of 8 patients and on the surface of non-necrotic myofibers in 4 of 8 patients. Five of 8 patients had abnormal capillary morphology, and 4 of 8 patients expressed class I MHC on the surface of non-necrotic myofibers., Conclusion: An anti-200/100-kd specificity defines a subgroup of patients with necrotizing myopathy who previously were considered to be autoantibody negative. We propose that these patients have an immune-mediated myopathy that is frequently associated with prior statin use and should be treated with immunosuppressive therapy.

Many drugs used for therapeutic interventions can cause unanticipated toxicity in muscle tissue, often leading to considerable morbidity. A drug-induced, or toxic, myopathy is defined as the acute or subacute manifestation of myopathic symptoms such as muscle weakness, myalgia, creatine kinase elevation, or myoglobinuria that can occur in patients without muscle disease when they are exposed to certain drugs. A brief review of agents with a known association with myotoxicity and the proposed mechanisms linked to that toxicity is outlined; however, the purpose of this review is to highlight recent discoveries and advances in the field of toxic myopathies that have practical implications for practicing physicians. Because many drug-related myopathies are potentially reversible at early stages, it is important for clinicians to recognize toxic myopathies early in their course to determine when to discontinue therapy and potentially prevent irreversible muscle damage.

The lung is one of the most common extra-muscular targets in idiopathic inflammatory myopathies (IIM) and interstitial lung disease (ILD) is a prevalent and often devastating manifestation of IIM. IIM-associated ILD (IIM-ILD) contributes to nearly 80% of the mortality in IIM with a reported prevalence of 65% of newly diagnosed IIM cases. Although ILD frequently accompanies clinical and laboratory findings of myositis, overt signs of muscle disease may be absent in the setting of significant lung disease. Understanding the varied scope of presentation of these diseases is essential to providing optimal patient care. This review will provide an in depth examination of ILD in IIM both from a rheumatologic and pulmonary perspective and will discuss the scope of disease, presenting features, genetic associations, pathogenesis, diagnosis, radiographic and histopathologic findings, along with biomarker assessment and a rationale for therapeutic intervention.

Objective: Pneumocystis pneumonia (PCP) occurs in immunocompromised hosts, in both the presence and absence of human immunodeficiency virus (HIV) infection, with substantial morbidity and a heightened mortality. We assessed practice patterns among rheumatologists for prescribing PCP prophylaxis., Methods: Invitations to an online international survey were e-mailed to 3150 consecutive members of the American College of Rheumatology., Results: Completed surveys were returned by 727 (23.1%) members. Among respondents, 505 (69.5%) reported prescribing prophylaxis. Factors associated with significantly higher frequency of prescribing PCP prophylaxis included female gender (OR 1.47, p = 0.03), US-based (OR 1.77, p = 0.004), academic-based (OR 2.75, p < 0.001), in practice less than 10 years (OR 4.08, p < 0.001), having previously treated PCP (OR 2.62, p < 0.001), and in a practice with a higher proportion of patients maintained on chronic glucocorticoids (OR 2.04, p < 0.001) or other immunosuppressant medications (OR 3.19, p = 0.003). In multivariate analysis, rheumatologists early in their careers and those with academic and US-based practices were more likely to prescribe prophylaxis. Among prescribers, the most important determinants for issuing prophylaxis were treatment regimen (68.6%), rheumatologic diagnosis (9.3%), and medication dosage (8.3%)., Conclusion: Nearly one-third (30%) of the rheumatologists surveyed reported that they never prescribed PCP prophylaxis. While the patient characteristics for which prophylaxis was prescribed varied widely, physician demographics were strongly predictive of PCP prophylaxis use. These findings suggest that development of consensus guidelines might influence clinical decision-making regarding PCP prophylaxis in HIV-negative patients with rheumatologic diagnoses.

Objective: Autoantibodies against the chromatin remodeler Mi-2 are found in a distinct subset of patients with dermatomyositis (DM). Previous quantitative immunoblotting experiments demonstrated that Mi-2 protein levels are up-regulated in DM muscle. This study was undertaken to define the population of cells expressing high levels of Mi-2 in DM muscle and to explore the regulation and functional role of Mi-2 during muscle regeneration., Methods: The expression of Mi-2 was analyzed by immunofluorescence microscopy in human muscle biopsy specimens. In an experimental mouse model, cardiotoxin was used to induce muscle injury and repair, and expression of Mi-2 during muscle regeneration was studied in this model by immunofluorescence and immunoblotting analyses. In addition, a cell culture system of muscle differentiation was utilized to artificially modulate Mi-2 levels during proliferation and differentiation of myoblasts., Results: In human DM muscle tissue, increased Mi-2 expression was found preferentially in the myofibers within fascicles affected by perifascicular atrophy, particularly in the centralized nuclei of small perifascicular muscle fibers expressing markers of regeneration. In injured mouse muscle tissue, Mi-2 levels were dramatically and persistently up-regulated during muscle regeneration in vivo. Premature silencing of Mi-2 with RNA interference in vitro resulted in accelerated myoblast differentiation., Conclusion: Expression of Mi-2 is markedly up-regulated during muscle regeneration in a mouse model of muscle injury and repair. It is also up-regulated in human DM myofibers expressing markers of regeneration. Results of the in vitro studies indicate that this protein may play a role in modulating the kinetics of myoblast differentiation. Our findings thus suggest that high levels of Mi-2 expression in muscle biopsy tissue from patients with DM reflect the presence of incompletely differentiated muscle cells.

Introduction: Previous studies of interstitial lung disease (ILD) suggest that prognosis and therapeutic response are influenced by the presence of underlying collagen vascular disease (CVD). Yet, what proportion of patients presenting with ILD have CVD is largely unknown. We sought to determine the frequency of a new CVD diagnosis in an ILD referral population., Materials/patients and Methods: We retrospectively studied 114 consecutive patients evaluated at the Johns Hopkins Interstitial Lung Disease Clinic for the development of CVD., Results: In this retrospective cohort, nearly one-third of the 114 patients with confirmed ILD satisfied published criteria for a CVD diagnosis. Seventeen (15%) patients were diagnosed with a new CVD as a direct consequence of their ILD evaluation. Patients with new CVD diagnosis were younger than those without new CVD diagnosis: 51.4years (95% CI 45-58years) and 60years (95% CI 57-63), respectively (p=0.01). Moreover, an ANA>or=1:640 (p=0.03) and elevated levels of creatine phosphokinase (CPK) or aldolase (p<0.001) were associated with a new CVD diagnosis., Conclusions: Unrecognized collagen vascular disease may be more common than previously appreciated among patients referred with ILD. High titer ANA and an elevated CPK or aldolase are associated with a CVD diagnosis in this referral population.

Objective: Early detection of renal involvement in lupus prevents poor outcomes. Although published guidelines recommend urine dipstick as an appropriate screening test and evidence suggests a majority of American rheumatologists use dipstick to screen for proteinuria, the performance of this diagnostic approach in lupus has not been reported. We examined the validity of qualitative urine dipstick versus quantitative 24-hour measurement to accurately detect proteinuria, including low-level proteinuria., Methods: We performed a diagnostic accuracy study using paired samples from the Johns Hopkins University School of Medicine and the Ohio State University School of Medicine lupus cohorts. All qualitative urine dipstick values were obtained within 1 day of a 24-hour urine collection., Results: We analyzed the performance of 3 urine dipstick assays to detect proteinuria compared to 24-hour protein/creatinine ratios, using 2224 dipstick measures from 296 patients. The sensitivity of a > or = 1+ dipstick result to detect quantitative proteinuria (> or = 0.50 g protein/g creatinine) was 82.7% for the Clinitek, 97.7% for the Atlas, and 85.5% for the Bayer assay. The corresponding sensitivity to detect low-level proteinuria, (0.50-0.99 g protein/g creatinine) was 63.1%, 96.4%, and 80.7%, respectively. The specificity to correctly exclude proteinuria (< 0.50 g protein/g creatinine) with negative/trace results was 86.1%, 62.2%, and 59.4%. There was considerable variability in the range of protein/creatinine ratios detected at each dipstick level of proteinuria., Conclusion: Urine dipsticks demonstrate substantial variability and often poor validity to accurately detect proteinuria at quantitative levels; this warrants further diagnostic evaluation. Clinicians should consider quantified proteinuria assays as a more accurate screening tool in the diagnostic evaluation of lupus nephritis.

Purpose of Review: The etiology and much about the pathogenesis of the inflammatory myopathies remain a mystery. In this review, we investigate recent research efforts to understand the pathogenesis of the diverse entities of polymyositis (PM), dermatomyositis (DM), and inclusion body myositis (IBM), diseases that result from interactions between environmental risk factors and genetic susceptibility., Recent Findings: Over the past year, there has been considerable progress toward better understanding of IBM, with relatively few developments toward understanding PM and DM. Although these diseases may share some common clinical phenotypic and serologic components, they differ on a molecular and cellular level., Summary: The need for definitive, safer therapies in these diseases makes vital the search for defining detailed pathogenesis of inflammation and muscle fiber damage at the molecular level.

Objective: To evaluate the 24-hour urine protein-to-creatinine (U pr:cr) ratio compared to 24-h urine total protein excretion as a measure of proteinuria in patients with lupus nephritis., Methods: Proteinuria in 8 patients with lupus nephritis treated with cyclophosphamide was monitored by total protein excretion and U pr:cr ratio in 24-h urine collections. A median of 16 measurements per patient were collected over a median of 47 months. Adequacy of the 24-h collection was assessed by comparing total urine creatinine to the predicted creatinine. Collections in which the difference between the predicted 24-h urine creatinine and the measured 24-h urine creatinine was greater than or equal to 20% were defined as inadequate collections., Results: Timed 24-h urine collections were frequently inadequate (30.2% of total collections were under-collections, while 14.3% were over-collections). We found 87.5% of patients had at least one under-collection whereas 75% had at least one over-collection. Correlations between total protein and U pr:cr ratio for individual patients ranged from 0.87 to 0.99 (mean 0.95). For the entire sample, the correlation (R2 = 0.89) of total urine protein to Upr:cr ratio was excellent. Excluding the 38 under-collections led to improvement in the overall correlation (0.94). Excluding the 18 over-collections led to a correlation of 0.89. Excluding both under-collections and over-collections led to a correlation of 0.94., Conclusion: In patients with lupus nephritis, the 24-h U pr:cr ratio is highly correlated with the 24-h urine protein excretion when the collections are adequate. The error of the estimate is higher when collections are poor.

The major inflammatory myopathies of adults-dermatomyositis, polymyositis and inclusion body myositis-are uncommon and can be difficult to distinguish from many conditions that mimic them clinically. They have a high morbidity; they are not infrequently the first sign of an associated malignancy; and they may be a part of another connective tissue disease. Their pathogenetic features suggest that they are different illnesses. Dermatomyositis and polymyositis are clearly inflammatory, both clinically and histologically, and both generally respond to therapy directed towards inflammation. Inclusion body myositis is now generally recognized as the most common myopathy presenting in patients over the age of 50 years, and it responds only modestly and sometimes not at all to immunosuppressive therapy. In this review, we have summarised the major newly recognized features of pathogenesis, the involvement of extramuscular organs, the differential diagnosis, diagnostic approaches and the main lines of therapy.