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Background: The implementation of more aggressive goals for low-density lipoprotein cholesterol lowering in subjects with type 2 diabetes (T2D) and the expected increase in the use of statins is likely to increase the concomitant use of thiazolidinediones (TZDs) and statins., Objective: This study evaluated whether concomitant use of TZDs and statins is associated with an increased risk of myopathic events in subjects with T2D., Methods: This was a nested case-control study in subjects with T2D. Cases and controls were identified from a cohort of 125,394 subjects with T2D in the Integrated Healthcare Information Services database. Each case with a myopathic event (rhabdomyolysis, myositis, myopathy, or myalgia) was matched to up to 6 controls by age (+/-5 years), sex, calendar year of diagnosis of a myopathic event, and length of follow-up in the database. Incident cases of myopathy were identified using the following International Classification of Diseases, Ninth Revision codes: 359.x for myopathy, 728.88 for rhabdomyolysis, and 729.1 for unspecified myalgia and myositis. Prescription claims were used as a proxy for drug exposure. Five categories of exposure were employed: statins only, TZDs only, concomitant TZDs and statins, other antidiabetic agents only, and neither statins nor antidiabetic agents. Exposure to statins and/or TZDs within 90 days before the case index date was defined as recent exposure, and exposure at any time before the case index date was defined as ever exposure. Concomitant exposure to TZDs and statins, either recent or ever, was defined by an overlap of at least 30 days in the days supply of TZDs and statins during the exposure period., Results: The 3696 cases of myopathy were matched with 21,871 controls. The adjusted odds ratio (OR) for myopathic events for ever exposure to concomitant TZDs and statins compared with statins alone was 1.03 (95% CI, 0.83-1.26). Compared with neither statins nor antidiabetic agents, ever use of statins alone was associated with an increased likelihood of myopathic events (adjusted OR=1.36; 95% CI, 1.12-1.64). The likelihood of myopathic events was not significantly different for TZDs compared with other antidiabetic agents., Conclusion: In this population of subjects with T2D, concomitant use of statins and TZDs was not associated with an increased risk of myopathic events beyond that conferred by statins alone.

Unlabelled: Transplant patients are at increased risk of developing dyslipidemia, which contributes to coronary artery disease and cardiovascular events. The purpose of this study was to explore documented adverse effects of liver transplant recipients receiving lipid-lowering therapies., Methods: A retrospective chart review of 69 liver transplant patients was conducted to evaluate the incidence of adverse effects, especially rhabdomyolysis and liver function abnormalities, in liver transplant patients treated with a lipid lowering agent (LLA). Data were collected from the time of initiation of LLA to 12 months later, looking at the type, dose, and duration of LLA, concurrent cytochrome P450 inhibitors, immunosuppression used, and laboratory parameters., Results: For HMG-CoA reductase inhibitor therapy, simvistatin was used in five (7.8%) patients, pravastatin in 40 (62.5%), fluvastatin in one (1.6%), atorvastatin in five (7.8%), and lovastatin in three (4.7%). Gemfibrozil, a fibric acid derivative, was employed as monotherapy in 10 (15.6%) of patients. There were five patients who received combination therapy with a fibric acid derivative, four (80%) with gemfibrozil + pravastatin, and one (20%) with gemfibrozil + simvastatin. Six patients studied had adverse effects, five (7.2%) with myalgia and one (1.4%) with myopathy. LLA monotherapy with either pravastatin or atorvastatin was used in these patients. The five patients with myalgia were on concurrent therapy with cyclosporin, and the patient with myopathy was on concurrent cyclosporin + diltiazem therapy, both of which are P450 inhibitors. One out of 23 patients on a non-immunosuppressant P450 inhibitor developed adverse effects. No significant elevation of alanine aminotransferase, aspartate aminotransferase, or alkaline phosphatase was noted in any patient., Conclusions: Overall, there was a general tolerability with a low incidence of adverse events, no incidence of severe complications, and no alterations in liver function tests in the study population with the use of LLA.

Background: Estimates of myopathy rates in the literature are based on adverse events reported in clinical trials, which may not be representative of the clinical practice setting., Objective: The objective of this study was to estimate the prevalence of myopathic events, particularly myalgia, myositis, and rhabdomyolysis in a community-based practice among a cohort of subjects with or without diabetes, some of whom received statin treatment., Methods: In this retrospective data analysis, we identified members of a health maintenance organization (HMO) who initiated statin treatment between 1997 and 2004 and classified them into 2 groups: those subjects with diabetes and those without. We matched them to an equal number of health plan members based on age group, diabetes diagnosis, and year of health plan enrollment. We defined 4 levels of myopathic events according to the American College of Cardiology, the American Heart Association, and the National Heart, Lung, and Blood Institute's definitions as follows: myalgia, mild myositis, severe myositis, and rhabdomyolysis. Subjects were observed for approximately 9 years. Prevalence rates were calculated by adjusting for known myopathic risk factors and also by utilizing Cox regression models to identify predictors of time for myopathic events., Results: Of the 35,413 HMO members initially assessed for inclusion, 32,225 were identified and classified into the 2 cohorts: diabetes (n = 10,247) and nondiabetes (n = 21,978). A greater proportion of statin initiators in both the diabetes (7.9% vs 5.5%; P < 0.001) and nondiabetes cohorts (9.0% vs 3.7%; P < 0.001) experienced myopathic events. However, 95% of events were myalgia or mild myositis. The prevalence of severe myositis was 0.4 per 1000 person-years (95% CI, 0.2-0.7) and 0.8 per 1000 person-years (95% CI, 0.6-1.1) among statin initiators with or without diabetes, respectively. By comparison, rates were 0.3 (95% CI, 0.1-0.5) and 0.2 (95% CI, 0.1-0.4) per 1000 person-years among nonstatin users with or without diabetes, respectively. Rates of rhabdomyolysis were 0.1 (95% CI, 0.1-0.3) and 0.2 (95% CI, 0.1-0.5) per 1000 person-years among statin and non-statin users with diabetes, respectively, and 0.2 (95% CI, 0.1-0.4) in both groups without diabetes., Conclusions: Statin initiation was associated with an approximate doubling of the risk for any myopathic event but did not appear to be associated with an increased risk for rhabdomyolysis in these patients. Because clinically significant elevations of creatine kinase levels were rare, statins appeared to be well tolerated in diabetic and nondiabetic patients who used them., (Copyright 2007 Excerpta Medica, Inc.)

Objective: To evaluate whether seasonal early environmental exposures might influence later development of autoimmune disease, by assessing distributions of birth dates in groups of patients with idiopathic inflammatory myopathies (IIMs)., Methods: We assessed birth patterns in groups of patients with juvenile-onset IIM (n = 307) and controls (n = 3,942) who were born between 1970 and 1999, and in groups of patients with adult-onset IIM (n = 668) and controls (n = 6,991) who were born between 1903 and 1982. Birth dates were analyzed as circular data. Seasonal clustering was assessed by the Rayleigh test, and differences between groups by a rank-based uniform scores test., Results: The overall birth distributions among patients with juvenile IIM and among patients with adult IIM did not differ significantly from those among juvenile and adult controls, respectively. Some subgroups of patients with juvenile IIM had seasonal birth distributions. Hispanic patients with juvenile-onset IIM had a seasonal birth pattern (mean birth date October 16) significantly different from that of Hispanic controls (P = 0.002), who had a uniform birth distribution, and from that of non-Hispanic patients with juvenile-onset IIM (P < 0.001), who had a mean birth date of May 2. Juvenile dermatomyositis patients with p155 autoantibody had a birth distribution that differed significantly from that of p155 antibody-negative juvenile dermatomyositis patients (P = 0.003). Juvenile IIM patients with the HLA risk factor allele DRB1*0301 had a birth distribution significantly different from those without the allele (P = 0.021). Similar results were observed for juvenile and adult IIM patients with the linked allele DQA1*0501, versus juvenile and adult IIM patients without DQA1*0501, respectively. No significant patterns in birth season were found in other subgroups., Conclusion: Birth distributions appear to have stronger seasonality in juvenile than in adult IIM subgroups, suggesting greater influence of perinatal exposures on childhood-onset illness. Seasonal early-life exposures may influence the onset of some autoimmune diseases later in life.

Objective: To determine whether interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) genes confer susceptibility for the idiopathic inflammatory myopathies (IIMs)., Methods: A large cross-sectional study of UK caucasian adults with polymyositis (PM, n = 101), dermatomyositis (DM, n = 94) and myositis overlapping with a connective tissue disease (myositis/CTD-overlap, n = 70) was completed. 177 ethnically matched controls were available for comparison. Single-nucleotide polymorphisms (SNPs) within intronic regions coding for IL-4, IFN-gamma and a microsatellite marker within intron 1 of the IFN-gamma gene were typed., Results: Strong linkage disequilibrium was present between SNPs in each gene. In the IFN-gamma gene, a weak allelic association was observed in PM versus controls at rs1861493 (odds ratio (OR) 1.6, 95% confidence interval (CI) 1.03 to 2.4). The microsatellite IFN-gamma CA(14) allele was associated with risk for IIMs overall (OR 3.3, 95% CI 1.4 to 7.8), the strongest association being observed within the anti-U1-ribonucleoprotein (RNP) group (OR 6.0, 95% CI 1.5 to 23.1), and persisting after adjustment for known myositis human leucocyte antigen (HLA) class II associations., Conclusions: Genetic markers in the IFN-gamma gene demonstrate significant allelic associations with the IIMs in a UK Caucasian population. The SNPs tested in this study within the region coding for IL-4 fail to show significant associations with susceptibility to IIM disease.

Background: Cases of pyomyositis and myositis have been increasing in frequency at Texas Children's Hospital (Houston) since 2000. The increase appears to correlate with the emergence of community-acquired methicillin-resistant Staphylococcus aureus (MRSA)., Methods: The medical records of patients with pyomyositis and myositis hospitalized at Texas Children's Hospital during the period from January 2000 through December 2005 were reviewed. Available S. aureus isolates were obtained for susceptibility testing, to determine the presence of pvl (lukS-PV and lukF-PV), and for pulsed-field gel electrophoresis analysis., Results: Forty-five previously healthy children with bacterial pyomyositis or myositis were analyzed. The causes were S. aureus (in 57.8% of children) and Streptococcus pyogenes (in 2.2%); 40.0% of children had negative culture results. The number of cases increased between 2000 and 2005, primarily as a result of an increase in the prevalence of community-acquired MRSA. The mean patient age was 5.5 years (range, 0.06-15 years). The thigh (40.0% of children) and pelvis (28.9%) were the most commonly affected sites. The mean abscess diameter was 3.5 cm. Eighteen children required at least 1 muscle drainage procedure. Of the 24 available S. aureus isolates (15 community-acquired MRSA isolates and 9 community-acquired, methicillin-susceptible S. aureus [MSSA] isolates), 16 were found to be USA300 by pulsed-field gel electrophoresis, and 17 carried pvl. Patients with community-acquired MRSA, USA300, and/or pvl-positive strains required more drainage procedures than did those with community-acquired MSSA, non-USA300, and/or pvl-negative strains (81% vs. 40% [P=.05], 82% vs. 29% [P=.02], and 81% vs. 38% [P=.07], respectively)., Conclusions: Community-acquired MRSA is an increasing cause of pyomyositis and myositis in children. Community-acquired MRSA, USA300, pvl-positive S. aureus isolates caused more severe disease than did community-acquired MSSA, non-USA300, and pvl-negative isolates, respectively.

The aim of this study was to assess the prevalence and the common type of malignancies in Korean patients with polymyositis (PM) and dermatomyositis (DM) and to evaluate the differences of clinical and laboratory findings between patients with malignancy and those without malignancy. Forty-one Korean patients, who were diagnosed as PM or DM, were enrolled in this study. They fulfilled the Bohan and Peter's criteria for a definite diagnosis of PM and DM. Patients with PM were 25 and those with DM were 16. Eleven out of 41 patients (26.8%) had malignancies. The malignancy was diagnosed simultaneously or later in 81.8% of patients with inflammatory myopathy (IM). The breast cancer was the most common malignancy. In this study, forty three years old as a screening age for malignancy had 88.9% sensitivity and 50.2% specificity. The serum levels of creatine kinase (CK) were significantly lower in patients with malignancy than those without malignancy.

Heart and skeletal muscle inflammation (HSMI) is a transmissible disease of farmed Atlantic salmon, Salmo salar L. It is characterized by significant epi-, endo- and myocarditis, as well as myositis, particularly involving red skeletal muscle. The aetiology of HSMI is currently unresolved, though a viral cause is suspected. Since its discovery in 1999, HSMI has become an increasing problem for the Norwegian farming industry, with some farms experiencing yearly outbreaks and subsequent economic losses. In the present study an Atlantic salmon farm was studied from December 2003 to April 2005. Samples from apparently healthy as well as clinically diseased fish were collected monthly and examined histopathologically. The first fish to be diagnosed with HSMI was sampled in May, 8 months after transfer to sea. A clinical outbreak of HSMI followed in June, when all fish in the sample had lesions consistent with HSMI. Subsequent samples revealed that cardiac lesions decreased in severity 2 months after the start of the outbreak, but that multiple foci of cellular infiltration and necrosis persisted throughout the year. There appeared to be a shift in lesion location from being most severe in the compact myocardium in early stages of disease to a greater involvement of the atrium and spongy layer of the ventricle in later samples. Late samples also showed increased fibrosis of cardiac tissue. In conclusion, HSMI appears to be a severe disease with elevated mortality, morbidity close to 100% and prolonged duration.

Objective: To describe the clinical, radiological and microbiological features of a series of patients diagnosed with pyomyositis in a tertiary care university-affiliated center over a 12-year period., Patients and Methods: The medical records of all patients diagnosed with pyomyositis between January 1992 and December 2003 were reviewed. The charts were retrieved from the hospital database. Data were extracted according to a standardized protocol and included clinical, radiological, laboratory and microbiological parameters., Results: A total of 54 patients (mean age, 50 years, 61% men) had pyomyositis. The most frequent predisposing factors were diabetes mellitus (22%) and traumatic injury (20%), followed by neoplasms (9%). Primary pyomyositis was diagnosed in 25 patients (55%), and a contiguous source of infection was detected in the remainder, with skin infection being the most frequent (40%). The most common presentation was isolated inflammatory signs with or without other symptoms (94%). Isolated fever was documented in only one patient. Ultrasonography was the most common diagnostic procedure performed (32%), followed by CT scanning (18%). Forty-five patients underwent a drainage procedure combined with antibiotic therapy. Pyomyositis was monomicrobial in 20 cases, and polymicrobial in 12. The most frequent pathogen was Staphylococcus aureus followed by coagulase-negative staphylococci (6 cases). Sepsis developed in 4 patients, and recurrence was observed in 8 (15%). Mortality was 10% (5 patients)., Conclusions: Pyomyositis is a relatively uncommon infection in temperate climates, and is often considered late in the diagnostic workup. Physicians should bear this disease in mind to avoid diagnostic delays and initiate prompt therapy, in order to improve the prognosis of these patients.

Most heart transplant candidates are equipped with left ventricular assist devices (LVADs). LVAD therapy is associated with characteristic psychiatric and psychosocial problems. To investigate the mental states of heart transplant candidates, psychiatric diagnosis, psychological or behavioral problems, and the need for treatment were evaluated around the time of registration to the waiting list and during follow-up. Saitama Medical University Hospital has been designated a hospital for heart transplantation since October 2002. The subjects were 14 heart transplant candidates (9 male candidates and 5 female candidates, mean age 29 years) at the hospital from September 1997 to October 2005. These 14 candidates were equipped with LVADs. The waiting periods on LVAD support were from 119 days to 1028 days, and the average waiting period was 313 days. Six candidates among the 14 had more than one DSM-IV diagnosis. Seven candidates were diagnosed with adjustment disorder, which was the most frequent diagnosis. Three candidates had depressive disorder, one had psychotic disorder, and one had dissociative disorder. Three candidates had acute cognitive dysfunction (delirium) due to their general medical condition. All three had other disorders with mainly psychological elements. Nine candidates (64%) were diagnosed with disorders with mainly psychological elements. Antipsychotics were used for the candidates in psychotic states and with delirium, and there was a need for crisis intervention. Antidepressants and antianxiety drugs were used for the candidates with depressive disorder; they needed intensive observation. Four candidates (28%) needed some attention and some antianxiety drugs or hypnotics. Psychiatric interventions were not necessary in five candidates (36%).

Pyomyositis is a primary infection of skeletal muscle not arising from contiguous infection, presumably hematogenous in origin, and often, but not invariably, associated with abscess formation. Classically, pyomyositis is an infection of the tropics, occurring in previously active and healthy young men. Pyomyositis in temperate countries is often regarded as an infection that occurs in hosts who are immunocompromised or otherwise debilitated. However,this distinction may be somewhat artificial, as tropical pyomyositis may be partly related to underlying infection with HIV or parasites, and temperate pyomyositis has been reported in healthy and athletic persons. This article discusses the pathogenesis, clinical presentation, diagnosis, and management of pyomyositis in the tropical and temperate settings.

The TT virus, a recently identified single-stranded DNA virus with unknown pathogenicity, has been shown to commonly infect humans. Viruses have been considered to contribute to disease pathogenesis in autoimmune disorders including idiopathic inflammatory myopathies (IIMs) and rheumatoid arthritis (RA). We assessed the prevalence of TTV infection in IIM compared with that in patients with RA and healthy blood donors. Detection of TTV was conducted by nested PCR and real-time PCR in the sera of 94 patients with IIM, 95 RA patients. and 95 age- and sex-matched healthy blood donors. Identity of the PCR products was confirmed by sequencing. TTV DNA was detected in 61 of 94 (64.9%) patients with IIM, in 64 of 95 (67.4%) patients with RA, and in 62 of 95 (65.3%; P > 0.05) healthy individuals. Age, sex, activity, or duration of disease had no influence on TTV positivity in either group. However, patients with severe IIM (n = 36) had a significantly higher rate of TTV infection (31/36, 86.1%) than patients with mild disease (30/58, 51.7%, P < 0.05, chi(2) = 10.0). Disease was considered severe in IIM when immunosuppressive treatment was necessary because of continuous high activity and/or serious inner-organ involvement despite corticosteroid treatment. In conclusion, although we found the detection rate of TTV similar in patients with idiopathic inflammatory myopathies and rheumatoid arthritis and comparable to that in healthy controls, our data suggest that infection with TT virus may result in a more severe disease in patients with idiopathic inflammatory myopathies.

Objective: To describe the clinical and laboratory features of benign acute childhood myositis., Methods: 40 children of BACM were seen during October 2001 to February 2002, 22 (52%) were male with mean age of 5.3 years. Duration of illness was 3.97 days. Preceding symptoms included fever, leg pain, vomiting and inability to walk. A provisional diagnosis of viral myositis was made in 26 (66%). Guillian Barre Syndrome was the most common referral diagnosis., Results: 11 (27.5%) children had leucopenia with lymphocytic response and 16 (40%) had thrombocytopenia. CRP was negative in 32 (80%). CPK was markedly elevated (more than 1000 IU/l) in 18 (45%) and more than 500 IU/l in 11 (27.5%) remaining between 200 to 500 IU/l. Associated features were hepatitis (elevated SGOT & SGPT) in 28 (70%) and shock in 5 (12.5%). Serological test were indicative of dengue virus (Elisa PAN BIO) in 20 (50%) of which 8 (25%) were primary dengue and 12 (30%) were secondary dengue. The outcome of therapy mainly supportive were excellent., Conclusion: Benign acute myositis occurs often in association with viral infection. In the present study, Dengue virus was positive in 20 (50%) children. Benign acute myositis can be differentiated from more serious causes of walking difficulty by presence of calf and thigh muscle tenderness on stretching, normal power and deep tendon reflex and elevated CPK.

Systemic lupus erythematosus (SLE), Sjogren's syndrome (SS), and dermatomyositis (DM)/polymyositis (PM) may be encountered in geriatric patients due to improved survival rates in patients with younger ages of onset or from elderly-onset (EO) disease. EO disease accounts for up to 20% of patients affected by these disorders, and is typically insidious rather than acute. Whereas SS and DM/PM are considered autoimmune diseases with distinct organ specificity, SLE is a systemic disorder that may affect multiple organ systems. Commonly used clinical and laboratory criteria for defining and diagnosing these diseases were largely developed for patients age <65, and need to be modified in the geriatric patient. Therapeutic strategies include attention to ongoing drug regimens, medical comorbidities, and the roles of fatigue, depression, and arthropathy. Each disease may be responsive to low-dose corticosteroids, with a role for first or second-line immunosuppressives as steroid-sparing agents.

Aim: To perform a clinical audit of all patients diagnosed with inflammatory myopathy in the North Canterbury region., Methods: A retrospective case note audit of patients with a discharge diagnosis of inflammatory myopathy from June 1989 to June 2001 was performed. The audit was based at Christchurch Hospital, New Zealand, which services a population of 430,000., Results: Of 77 case notes reviewed, 44 patients were identified who were considered to fulfil clinical criteria for inflammatory myopathy. There was a female preponderance (80% female, 20% male). Diagnostic categories in descending order of frequency included: dermatomyositis (41%), polymyositis (39%), inclusion body myositis (IBM) (14%) and overlap syndromes (6%). Malignancy-associated myositis occurred in 20% overall (dermatomyositis 11%, polymyositis 9%). Delays in diagnosis and late age at presentation (average 72 years) were seen in the IBM group. Proximal limb weakness was common, but not universal at presentation (80%). A muscle biopsy was performed in all patients and electromyography in 82%. All were treated with high dose prednisone (0.5-1 mg/kg) of whom 29% were maintained on prednisone alone. Immunosuppressives/immunomodulators used included: azathioprine (58%), methotrexate (31%), intravenous immunoglobulin (13%), chlorambucil (13%), and cyclophosphamide (9%). Thirteen patients (42%) required more than one agent, with three trialling five agents. There were 59 relapses in 20 patients (45%), with mean time to first relapse of 7.8 months. At audit completion, 33% had deceased with malignancy and respiratory failure the main causes., Conclusion: Inflammatory myopathy is a challenging condition in both diagnosis and management. Our audit has shown delays in the diagnosis of IBM, a relatively high incidence of malignancy and a notable risk of relapse and mortality.

Objective: Tropical pyomyositis, a bacterial muscular infection, has been reported frequently from tropical and subtropical zones. However, there are only a few reports from Mexico., Materials and Methods: We present a prospective study of tropical pyomyositis cases in three secondary- and tertiary-care hospitals in Veracruz, Mexico between August 1985 and December 2000., Results: Tropical pyomyositis was more common in young adults, male-to-female ratio being 2.2:1. Principal features were muscle pains, fluctuanct muscular mass, and fever. Tropical pyomyositis was associated with recent muscular trauma and/or pyodermitis in 67% of cases. 60% of admissions presented invasive clinical stage of the disease, and fewer of 20% of cases presented multiple muscular involvement. Staphylococcus aureus was the most common etiologic agent. Most frequent complications were pleuropulmonaries. Only one patient, who had septicemia and multiple organ failure, died., Conclusions: Tropical pyomyositis is rare in healthy individuals and requires high clinical suspicion. Prognosis is generally favorable after surgical drainage and adequate antimicrobial therapy.

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.

The incidence of reported bacterial pyomyositis is increasing in the United States, especially among immunocompromised persons. This review summarizes all reported cases of pyomyositis among human immunodeficiency virus (HIV)-infected persons worldwide and HIV-negative persons in the United States since 1981. During the era of combination antiretroviral therapy, bacterial pyomyositis among HIV-infected persons typically occurred in those with end-stage acquired immunodeficiency syndrome. Among non-HIV-infected patients, about half have a serious underlying medical problem, most commonly diabetes mellitus, malignancy, or a rheumatologic condition. These patients are more likely to have a gram-negative infection, a normal white blood cell count, multifocal involvement, or higher mortality than those without an underlying medical condition. The characteristics of cases in temperate areas are similar to tropical cases, except that the former occurs more often in immunocompromised persons; this may change with the HIV epidemic in tropical regions., (Copyright 2004 Elsevier Inc.)

Objective: Microchimeric cells have been identified in lesions and peripheral blood of patients with systemic sclerosis (SSc) and idiopathic inflammatory myopathies (IIM), and HLA-DQA1*0501 is a risk factor for these diseases in some populations. Furthermore, DQA1*0501 has been associated with T lymphocyte microchimerism in SSc. To better define the strength of this association, we assessed the relationship among DQA1 alleles and microchimerism., Methods: DNA from whole peripheral blood or magnetically sorted T cells was tested for microchimeric cells by polymerase chain reaction of the Y chromosome or of HLA-Cw in 87 SSc patients, 28 juvenile IIM patients, and 88 healthy controls. Thirty-seven mother-son pairs were also analyzed for microchimerism and DQA1*0501., Results: We were unable to demonstrate that DQA1*0501 is associated with microchimerism in T lymphocytes or in whole peripheral blood DNA in patients with SSc or juvenile IIM or in healthy individuals. In the 37 mother-son pairs, we were unable to demonstrate an association of DQA1*0501 with microchimerism in peripheral blood DNA or T lymphocytes, and compatibility between the donor's and recipient's HLA alleles did not influence microchimerism in the recipient., Conclusion: These data suggest that HLA-DQA1 alleles do not appear to play a role in the persistence of microchimerism in the peripheral blood or T lymphocytes of patients with selected autoimmune diseases or in healthy individuals.

The inflammatory myopathies - myositis - encompass a heterogeneous group of chronic muscle disorders of unknown origin and with varying prognoses. New clinical phenotypes of myositis have been identified since the most widely used classification criteria were proposed in 1975. Based on clinical and histopathological features, inclusion body myositis was identified. Furthermore, the myositis-specific autoantibodies may also identify different clinical phenotypes and serve as prognostic markers. The different classifications and inclusion criteria that have been used in different studies make some epidemiological data uncertain. In order to improve our knowledge of causative factors, as well as of pathogenic mechanisms, there is a need for revision and also for an international acceptance of the classification criteria. During recent years, our knowledge has increased regarding the role of some genetic and environmental factors that could affect susceptibility for developing myositis as well as the prognosis. Whether there is an association between myositis and malignancies has been a subject of controversy for many years and recent epidemiological data have brought some clarification on this issue.

Epidemiologic studies have helped to define the prevalence and incidence of PM, DM, and IBM and have highlighted differences in risk between men and women and in the age at onset for the different forms of myositis. Additionally, these studies have shown that there is a substantially higher risk of PM and DM in certain racial groups which is likely to be genetically determined. These differences are all likely to be fundamental in terms of the pathogenesis of these diseases but, as yet, their full significance remains uncertain. They do, however, suggest that the interplay between genetic and environmental initiating factors is different in the three disorders. Additional population-based studies in homogeneous racial groups, in parallel with studies of susceptibility genes for autoimmune disease, such as those encoding the MHC and inflammatory cytokines, are needed to throw further light on the role of genetic factors in the pathogenesis of the IIMs [47]. Because of the paucity of epidemiologic data on IBM, further studies are required to determine the degree of variation in prevalence in different populations and racial groups, as well as the consistency of the male association and age spectrum of manifestations of the disease. The particularly strong association with DR3 in this form of IIM [48] clearly points to the importance of genetic factors in pathogenesis, but further studies of DR3-associated genes in the MHC and of other candidate genes are needed to define more precisely the genes that convey susceptibility to the disease in different racial groups. Epidemiologic studies also have the potential to identify environmental factors that may play a part in disease initiation in genetically susceptible individuals. Seasonal patterns of disease onset have been reported, particularly in patients with DM [49-51] as well as seasonal variation in the frequency of relapses [52], pointing to the probable involvement of intercurrent infections, ultraviolet light exposure, or other environmental factors in disease initiation and reactivation. Further prospective studies are required to determine the contribution of environmental exposures and how they interact with genetic susceptibility factors to lead to myositis. One of the major limitations of a number of the previous epidemiologic studies is the lack of precision in the diagnostic criteria used and the classification of cases of IIM. The Bohan and Peter criteria [1] which were used in most studies after 1975, were introduced before IBM was recognized as an entity distinct from PM; most of the published incidence and prevalence figures for PM are therefore likely to be inaccurate. Multicentered, interdisciplinary, prospective studies, incorporating comprehensive clinical, laboratory, and pathologic information, are needed to develop and validate better diagnostic and classification criteria and to determine the true prevalence and incidence of the many forms of IIM.

Objective: To describe the clinical spectrum of inflammatory myopathies at a referral hospital in South India., Methods: Patients were assessed for the pattern of muscle involvement, for the presence of arthritis, Raynaud's phenomenon, interstitial lung disease (ILD) and cardiac involvement. Muscle enzymes, electromyogram (EMG) and muscle biopsies were done., Results: Eighty seven patients with inflammatory myopathies were encountered over 10 years. These included 24 with adult polymyositis, 26 with adult dermatomyositis, one with amyopathic dermatomyositis, five with juvenile myositis, one with dermatomysitis following carcinoma breast and 30 with overlap with other connective tissue diseases. There was a female preponderance (M:F = 1:2.35) except in juvenile myosits group (M:F = 1.5:1). The mean age of onset in years was 33.26 in adult polymyositis, 35.03 in adult dermatomyositis, 7.4 in juvenile dermatomyositis, 42 in malignancy-associated dermatomyositis and 25.51 in the overlap group. Proximal muscle weakness was seen in 98.8% patients, dysphagia in 33.3%, distal muscle weakness in 12.5%, respiratory muscle weakness in 9.2% and dysphonia in 4.6%. Other features included arthritis 35.63%, interstitial lung disease (ILD) 9.2%, Raynaud's 5.7%, myocarditis 4.6% and conduction disturbances 1.15%. Eleveated muscle enzymes were seen in 85.1% patients. Eletromyogram was positive in 66.6%. Muscle biopsy was positive in 85.29%. Anti-nuclear antibody was positive in 67.24%. All received steroids, non-responders needed methotrexate (13 patients) or azathioprine (11 patients). Death occurred in 10 (seven with dermatomyositis predominantly due to respiratory involvement and three with overlap)., Conclusion: There was female preponderance except in juvenile myositis group. Proximal muscle weakness was the commonest feature. ILD was the commonest respiratory problem, while myocarditis was the commonest cardiac problem seen. Response to therapy and prognosis in polymyositis were good with no mortality during the study period. Death in the dermatomyositis group was mainly due to respiratory involvement.

Objective: As part of a larger, worldwide study of the ethnogeography of myositis, we evaluated the clinical, serologic, and immunogenetic features of Mestizo (Mexican and Guatemalan) and North American Caucasian patients with idiopathic inflammatory myopathy (IIM)., Methods: Clinical manifestations, autoantibodies, HLA-DRB1 and DQA1 alleles, and immunoglobulin Gm/Km allotypes were compared between 138 Mestizos with IIM and 287 Caucasians with IIM, using the same classification criteria and standardized questionnaires., Results: IIM in Mestizo patients was characterized by a higher proportion of dermatomyositis (69% of adult Mestizos versus 35% of adult Caucasians; P < 0.001) and anti-Mi-2 autoantibodies (30% versus 7% of adults, respectively, and 32% versus 4% of children, respectively; P < 0.01). Genetic risk factors also differed in these populations. Whereas Mestizos had no HLA risk factors for IIM, HLA-DRB1*0301, the linked allele DQA1*0501, and DRB1 alleles sharing the first hypervariable region motif (9)EYSTS(13) were major risk factors in Caucasian patients with IIM. Furthermore, different HLA-DRB1 and DQA1 alleles were associated with anti-Mi-2 autoantibodies (DRB1*04 and DQA1*03 in Mestizos and DRB1*07 and DQA1*02 in Caucasians). Immunoglobulin gamma-chain allotypes Gm(1), Gm(17) (odds ratio for both 11.3, P = 0.008), and Gm(21) (odds ratio 7.3, P = 0.005) and kappa-chain allotype Km(3) (odds ratio 7.3, P = 0.005) were risk factors for IIM in Mestizos; however, no Gm or Km allotypes were risk or protective factors in Caucasians. In addition, Gm and Km phenotypes were unique risk factors (Gm 1,3,17 5,13,21 and Gm 1,17 23 21 and Km 3,3) or protective factors (Km 1,1) for the development of myositis and anti-Mi-2 autoantibodies (Gm 1,2,3,17 23 5,13,21) in adult Mestizos., Conclusion: IIM in Mesoamerican Mestizos differs from IIM in North American Caucasians in the frequency of phenotypic features and in the immune-response genes predisposing to and protecting from myositis and anti-Mi-2 autoantibodies at 4 chromosomal loci. These and other data suggest the likelihood that the expression of IIM is modulated by different genes and environmental exposures around the world.

The seasonal occurrence of relapses was analysed retrospectively in a group of 53 patients with treated dermatomyositis (DM) or polymyositis (PM). In DM, the incidence of both myositic and cutaneous relapses was highest in summer whereas in the PM group relapses was more evenly distributed throughout the seasons but lowest in summer. The present findings suggest that environmental factors such as intercurrent infections and light exposure may be involved in reactivating the disease process and causing relapses in DM but less so in PM. Further prospective studies are needed to assess the role of environmental factors in the initiation and reactivation of the inflammatory myopathies.

Macrophagic myofasciitis (MMF) is an emerging condition of unknown cause, detected in patients with diffuse arthromyalgias and fatigue, and characterized by muscle infiltration by granular periodic acid-Schiff's reagent-positive macrophages and lymphocytes. Intracytoplasmic inclusions have been observed in macrophages of some patients. To assess their significance, electron microscopy was performed in 40 consecutive cases and chemical analysis was done by microanalysis and atomic absorption spectrometry. Inclusions were constantly detected and corresponded to aluminium hydroxide, an immunostimulatory compound frequently used as a vaccine adjuvant. A lymphocytic component was constantly observed in MMF lesions. Serological tests were compatible with exposure to aluminium hydroxide-containing vaccines. History analysis revealed that 50 out of 50 patients had received vaccines against hepatitis B virus (86%), hepatitis A virus (19%) or tetanus toxoid (58%), 3-96 months (median 36 months) before biopsy. Diffuse myalgias were more frequent in patients with than without an MMF lesion at deltoid muscle biopsy (P < 0.0001). Myalgia onset was subsequent to the vaccination (median 11 months) in 94% of patients. MMF lesion was experimentally reproduced in rats. We conclude that the MMF lesion is secondary to intramuscular injection of aluminium hydroxide-containing vaccines, shows both long-term persistence of aluminium hydroxide and an ongoing local immune reaction, and is detected in patients with systemic symptoms which appeared subsequently to vaccination.

Idiopathic inflammatory myositis in children includes multiple disease entities, but is primarily made up of juvenile dermatomyositis and, to a lesser degree, juvenile polymyositis. Much new information has been published in the last few years about these diseases, including the epidemiology, pathogenesis, clinical diagnosis, and outcomes and treatment. This includes information on onset of symptoms, potential inciting agents, and regional differences. Exciting data have emerged in our understanding of the immune response gene associations and the description of chimerism in children with these disorders. Finally, new advances in clinical evaluations and outcomes have been described as well as new treatment protocols to provide a more effective therapy with less toxicity. Continued investigation is needed to further understand these diseases, but great strides are being made in our understanding and ability to care for children with idiopathic inflammatory myositis.

From January 1988 to December 1999, 43 adults with pyomyositis were managed at Ahmadu Bello UniversityTeaching Hospital, Zaria, Nigeria. Staphylococcus aureuswas the most commonly cultured organism (92.5%). All the 41 patients responded well to incision and adequate drainage, antibiotics and partial thickness skin grafting in 10 patients (23.2%).Two patients (4.65%) died from septicaemia, while being resuscitated.

Objective: Tropical pyomyositis (TP), a disease of varied aetiology, has been reported frequently from Africa and Latin America. However there are only a few reports from India., Material and Methods: Between January 1992 to June 1999, 26 patients with TP were admitted to Post Graduate Institute of Medical Education and Research Chandigarh, a tertiary care centre in north-west India and formed the study material., Results: The disease was more common in young adults with male to female ratio being 5:2. In majority, presenting features were muscle pains (100%) and fever (81%). The diagnosis was confirmed by aspirating pus from the involved muscle. The pus grew organisms in 41.7% patients and methicillin sensitive Staphylococcus aureus was the commonest causative organism. Blood cultures were positive in 14.3% of cases. The common complications were bronchopneumonia (23.1%), empyema (19.2%) and venous thrombosis (15.4%). In three patients, the disease occurred in association with tuberculosis of dorsal-lumbar spine. The overall mortality was low (7.7%)., Conclusions: TP is not an uncommon disease in India. Though the presenting features were similar to earlier studies, complications varied and mortality was low. An early recognition and aggressive treatment helps in decreasing morbidity and mortality.

A number of lines of investigation suggest that, as is likely the case for other autoimmune diseases, the idiopathic inflammatory myopathies (IIM) develop as a result of specific environmental exposures in genetically susceptible individuals. Current data imply that multiple genes are involved in the etiology of these complex disorders. Targeted gene studies and whole genome approaches have begun to identify several genetic risk factors for autoimmune diseases, but the rarity and heterogeneity of the IIM have limited our knowledge of their associated genes. Current findings suggest that human leukocyte antigen (HLA) genes on chromosome 6, particularly HLA DRB1*0301 and the linked allele DQA1*0501, have the strongest associations with all clinical forms of IIM in white patients. Different HLA alleles, however, may confer risk or protection for myositis in distinct ethnic, serologic, and environmental exposure groups. Non-HLA genetic risk factors, which have been documented for other autoimmune diseases, are now being identified for the IIM. These include polymorphic genes encoding immunoglobulin heavy chains (defined by serologic markers known as Gm allotypes), cytokines and their receptors, and certain proteins that accumulate in the myocyte vacuoles of inclusion body myositis patients. Selected allelic polymorphisms of interleukin-1 receptor antagonist variable number tandem repeats and genes for tumor necrosis factor alpha and interleukin-1 alpha also have recently been associated with IIM. The pathogenic bases for the differences among the many clinically, pathologically and immunologically defined syndromes known as the IIM will be elucidated through a better understanding of the multiple genes that define risks for their development, as well as through investigations of gene-gene and gene-environment interactions.

A 10-year retrospective review was conducted to ascertain the prevalence of inclusion body myositis (IBM) in Western Australia. Seventeen patients with sporadic IBM aged 45-90 years were identified and the prevalence of IBM was calculated to be 9.3 x 10(-6). The prevalence was higher in men (10.9 x 10(-6)) than in women (7.7 x 10(-6)). The mean age of onset of IBM was 56.6 years, and the mean delay between onset of symptoms and diagnosis was 4.4 years. The age-adjusted prevalence over the age of 50 years was 35.3 x 10(-6). The results suggest a higher prevalence of IBM than has previously been reported., (Copyright 2000 John Wiley & Sons, Inc.)

Myositis associated with infection by Ichthyophonus-like organisms was diagnosed in 35 of 260 (13%) wild amphibians collected in Quebec, Canada, from 1959 to 1964 (n = 30), and 1992 to 1999 (n = 230). Infection was diagnosed in 17 green frogs Rana clamitans, 9 wood frogs R. sylvatica, 4 red-spotted newts Notophthalmus viridescens, 3 bullfrogs R. catesbeiana, 1 spring peeper Pseudacris crucifer, and 1 pickerel frog R. palustris. The spring peeper and one of the bullfrogs were collected in 1964 from the Mont Saint-Hilaire Biosphere Reserve, indicating long-term presence of the organism. Spores of the organisms invaded striated muscle fibers and were associated with variable degrees of granulomatous and eosinophilic inflammation. Infection was considered fatal in 2 green frogs, 1 wood frog, and 1 red-spotted newt. It was considered potentially significant in 3 additional green frogs in which up to 100% of the fibers of some muscles were replaced by spores associated with a severe granulomatous reaction. Ultrastructural features of Ichthyophonus-like spores included a thick trilaminated wall, a paramural cytoplasm, multiple nuclei, oval mitochondria with short tubulo-vesicular cristae and numerous ribosomes. This report represents 4 new host records and shows that ichthyophonosis is enzootic in amphibians from Quebec.

Background: About 50% of patients with thymoma have paraneoplastic myasthenia gravis (MG). Myositis and myocarditis or neuromyotonia (NMT) will also develop in some. Patients with thymoma-associated MG produce autoantibodies to a variety of neuromuscular antigens, particularly acetylcholine receptor (AChR), titin, skeletal muscle calcium release channel (ryanodine receptor [RyR]), and voltage-gated potassium channels (VGKC)., Objective: To examine whether neuromuscular autoantibodies in patients with thymoma correlate with specific clinical syndromes., Methods: Serum and plasma samples from 19 patients with thymoma-associated MG, of whom 5 had myositis and 6 had NMT, underwent testing for antibodies to AChR, titin, RyR, and VGKC., Results: Antibodies to AChR and titin were found in 19 and 17 patients, respectively. Antibodies to RyR correlated with the presence of myositis (P = .03); they were found in all 5 patients with myositis and in only 1 patient with NMT, but also in 4 of 8 patients with neither disease. Antibodies to VGKC were found in 4 patients with NMT, 1 of 3 patients undergoing testing for myositis, and 2 of 7 patients undergoing testing with neither comorbidity. Presence of RyR antibodies correlated with high levels of titin antibodies., Conclusions: The results appear to distinguish partially between 3 groups of patients with thymoma-associated MG: the first with RyR antibodies and myositis or myocarditis, the second with NMT without RyR antibodies, and the third without RyR antibodies, myositis, or NMT. Differences in the thymoma may underlie these pathologic associations.

Seven members of a 15-man U.S. military team that had operated in rural Malaysia developed an acute illness consisting of fever, myalgias, bronchospasm, fleeting pruritic rashes, transient lymphadenopathy, and subcutaneous nodules associated with eosinophilia, elevated erythrocyte sedimentation rate, and elevated levels of muscle creatinine kinase. Sarcocysts of an unidentified Sarcocystis species were found in skeletal muscle biopsies of the index case. Albendazole ameliorated symptoms in the index case; however, his symptoms persisted for more than 5 years. Symptoms in 5 other men were mild to moderate and self-limited, and 1 team member with laboratory abnormalities was asymptomatic. Of 8 team members tested for antibody to Sarcocystis, 6 were positive; of 4 with the eosinophilic myositis syndrome who were tested, all were positive. We attribute this outbreak of eosinophilic myositis to accidental tissue parasitism by Sarcocystis.

Objective: To determine the incidence of idiopathic inflammatory myopathies (IIM) in Victoria, Australia, and look for evidence of space-time or spatial clustering., Methods: Cases of IIM diagnosed between 1989 and 1991 were identified by muscle biopsy and hospital discharge diagnosis review. Diagnosis was verified by medical record review and included if Bohan and Peter criteria for definite or probable disease were met. The pair-wise Euclidean distances between cases' residences were computed using grid references, and temporal distances were calculated between biopsy dates. The Mantel test for space-time clustering was computed. Each patient was also characterized by statistical local area (SLA) according to place of residence. For each SLA, the expected annual incidence of IIM was calculated, based upon its population distribution, and these were compared to the observed annual incidence. Confidence intervals for the true rate ratio (RR) for each SLA were calculated assuming a Poisson distribution, and the level of heterogeneity in the data was examined by calculation of a chi-squared for homogeneity., Results: Ninety-four cases met inclusion criteria for an annual incidence of 7.4 (95% CI 6.0-9.0) per million person-years. No space-time clustering was found (z = -0.434, p = 0.665), but there was evidence of spatial clustering. A total of 67 observed cases were distributed among 58 urban SLA. Four SLA had a greater than expected incidence of myositis (95% Poisson based CI excluded 1), accounting for 20 of the observed cases., Conclusion: The incidence of IIM in Australia is higher than most previous population based estimates. The finding of spatial clustering supports the hypothesis that environmental factors may be important in the pathogenesis of these diseases.

Tropical pyomyositis (TP) is a microbial infection involving one or more skeletal muscles that rapidly leads to abscess. The most common infectious agent is Staphylococcus aureus. Since muscle tissue is highly resistant to infection, occurrence of TP is contingent upon one or more compromising factors such as trauma, skin lesions, parasitosis, or malnutrition. HIV infection is currently a major factor in the occurrence of TP. While Staphylococcus aureus accounts for 80% of cases, other microbial agents have been identified including gram-positive cocci and gram-negative bacilli. TP is endemic in intertropical zones of Africa and Latin America and in island areas of the Pacific Ocean. However a growing number of non-tropical cases have been reported in association with AIDS. The most frequent presentation is single-muscle involvement in the thighs, calves, and buttocks. The symptomatic phase or suppurative phase is almost always associated with hyperthermia. The infected muscle indurates prior to development of characteristic fluctuance. Hemocultures are seldom positive but needle aspiration may confirm diagnosis. Ultrasound imaging can allow early detection. Severe sepsis or cardiovascular, renal, or pleuropulmonary complications are observed in 10% of cases. Treatment is antibiotic therapy with penicillin M and surgical drainage or needle puncture of abscess cavities. Prognosis is generally favorable even in HIV-infected patients.

Pathogenesis of Aino virus (AIV), a suspected causative agent of congenital abnormalities of calves, has not yet been established by experimental infection of dams. To investigate the pathogenesis, 10(3) median tissue culture infective doses per 0.2 ml of AIV strain JaNAr 28 was inoculated into the yolk sac of 8-day-old chick embryos. At 4, 7, 10, and 13 days post-inoculation (PI) 20 eggs were opened and macro- and microscopic studies combined with virus recovery and immunohistochemical detection of the virus antigen were performed. At 7 to 13 days PI chick embryos manifested marked hydranencephaly, cerebellar hypoplasia, arthrogryposis, and scoliosis, with the highest incidences of 86.7%, 73.3%, 80.0%, and 20.0%, respectively. At 4 days PI the viral antigen was found in nerve cells, gitter cells in mild necrotic foci of the central nervous system (CNS), degenerative myotubules, and macrophages in the interstitium, which was associated with the early phase of AIV-induced encephalitis and polymyositis, with occasional accompanying hemorrhage and clumping of myotubular fragments. From 7 to 10 days PI, AIV antigen increased markedly in the liquefactive necrosis and in both degenerative and normal-looking myotubules in conjunction with developing hydranencephaly and arthrogryposis. The encephalitis and myositis had a tendency to mitigate by 10 days PI, coincident with a slight decrease in amount of AIV antigen. At 13 days PI there was almost no detectable AIV antigen in CNS and skeletal muscles, probably due to depletion of cells having affinity to AIV.

Bacterial complications of varicella in 84 patients younger than 16 years of age (48 females; median age, 2.9 years) who required hospitalization between 1985 and 1995 were retrospectively analyzed. The purpose of the study was to describe demographics, clinical manifestations, bacteriology, and factors affecting outcome. Seventy-six percent of patients were younger than 5 years of age. The eldest children in households were significantly underrepresented (P = .00025). Skin infections occurred in 61 patients (73%), and deep-seated infections and/or shock occurred in 23 (27%). The latter complications were significantly associated with thrombocytopenia (P = .011) and bacteremia (P = .014) at the time of admission, prolonged fever (P = .001), prolonged hospitalization (P < .0001), intensive care management (P < .0001), and fatal outcome (P = .019). Group A beta-hemolytic streptococcus (59% of isolates) and Staphylococcus aureus (28%) were the predominant isolates. Before and after 1990, five (31%) of 16 and 13 (62%) of 21 streptococcal complications, respectively, were invasive infections (P = .09). These data underscore the need for universal immunization against chickenpox.

Tropical pyomyositis is a rare cause of multiple abscesses of skeletal muscle. The entity is rare in temperate climates and, as its name suggests, is more common in areas such as the tropics and South Pacific. Staphylococcus aureus is the most common cause of infection. Therapy is aggressive, with surgical debridement and drainage followed by antibiotics. We report an unusual case of tropical myositis which simulated tumor recurrence in a patient without the typical risk factors associated with tropical pyomyositis.

Pyomyositis is caused by staphylococci in 70% to 90% of patients. We report a case of pneumococcal pyomyositis (PP), review the 11 cases previously published, and compare the features of pneumococcal pyomyositis with those of classic (nonpneumococcal) pyomyositis. Several clinical characteristics have been identified that are notably different in both groups. Psoas muscle involvement was observed in two thirds of the patients with PP, and a source for the infection was identified in half of the patients. Patients with PP were older than those with classic pyomyositis. Men were affected less often than women with PP, but the opposite was the rule in classic pyomyositis. The systemic response to the infection was more prominent in patients infected with pneumococci than from other causes. Most patients with PP were successfully treated with antibiotics and drainage. Secondary meningitis was observed in 3 patients with psoas muscle abscess caused by pneumococci. Mortality is low in pyomyositis regardless of the causative pathogen.