Symptomatic myopathies in sarcoidosis: disease spectrum and myxovirus resistance protein A expression.

OBJECTIVES: Symptomatic myopathy in sarcoidosis patients is not always due to sarcoid myopathy (ScM). We investigated the clinical and pathological spectrum including myxovirus resistance protein A (MxA) expression among sarcoidosis patients. METHODS: We reviewed the Mayo Clinic database (May 1980-December 2020) to identify sarcoidosis patients with myopathic symptoms and pathological evidence of myopathy. RESULTS: Among 5885 sarcoidosis patients, 21 had symptomatic myopathy. Eight carried a diagnosis of sarcoidosis 5.5 years (median) prior to myopathy onset. Eleven patients had ScM. The remaining had non-sarcoid myopathies (five IBM, one immune-mediated necrotizing myopathy, one non-specific myositis, two non-specific myopathy and one steroid myopathy). Estimated frequency of IBM is 85 per 100 000 sarcoidosis patients. The following features were associated with non-sarcoid myopathies (P < 0.05): (i) predominant finger flexor and quadriceps weakness, (ii) modified Rankin scale (mRS) >2 at time of diagnosis, (iii) creatine kinase >500 U/l, and (iv) absence of intramuscular granulomas. Sarcoplasmic MxA expression was observed in scattered myofibres in three patients, two of whom were tested for DM-specific autoantibodies and were negative. Immunosuppressive therapy led to improvement in mRS ≥1 in 5/10 ScM, none of the five IBM, and 3/3 remaining patients with non-sarcoid myopathies. DISCUSSION: Symptomatic myopathy occurred in 0.36% of sarcoidosis. IBM was the second most common cause of myopathies after ScM. Frequency of IBM in sarcoidosis is higher than in the general population. Recognition of features suggestive of alternative aetiologies can guide proper treatment. Our findings of abnormal MxA expression warrant a larger study.

Cancer and immune-mediated necrotizing myopathy: a longitudinal referral case-controlled outcomes evaluation.

OBJECTIVES: To investigate immune-mediated necrotizing myopathy (IMNM) association with cancer and its clinical implications. METHODS: IMNM cases were identified 1 January 2000 to 31 December 2020 matching sex and age controls (4:1). RESULTS: A total of 152 patients with IMNM were identified and among serologically tested, 60% (83/140) were HMGCR-IgG+, 14% (20/140) were SRP-IgG+ and 26% (37/140) were seronegative. Cancer rates were not significantly different between serological subgroups; 18.1% (15/83) HMGCR-IgG+, 25% (5/20) SRP-IgG+ and 30% (11/37) seronegative (P = 0.34). Cancer screening was performed within 12 months from IMNM diagnosis in 88% (134/152) (whole-body CT plus FDG-PET CT in 53, CT alone in 72 and FDG-PET alone in 9). FDG-PET/CT was positive in 73% (25/34) of cancers. Increasing age was the only risk associated with cancer (P = 0.02). The odds of developing cancer at ±3 or ±5 years from IMNM diagnosis was not higher than controls (OR = 0.49; CI: 0.325-0.76). Lifetime IMNM diagnosis of cancer was less compared with controls (OR = 0.5 CI: 0.33-0.78, P = 0.002). Most patients responded to treatment (137/147, P < 0.001). Death and treatment response did not significantly differ between cancer [23% (8/34); 88% (29/33)] and non-cancer patients [19% (23/118); 92% (108/118)]. In total, 13% (20/152) of patients died during follow-up compared with 14% (41/290) of medicine and 16% (46/290) of neurology controls (P = 0.8). Seropositives had greater life expectancy than seronegatives (P = 0.01). CONCLUSIONS: Greater cancer risk is not observed in IMNM vs controls. Cancer screening in IMNM should be individualized based on age-personal and family history, including consideration of FDG-PET/CT. Immune-treatment response did not differ with cancer.

Do histopathological features correlate with systemic manifestations in dermatomyositis? Analysis of 42 skin biopsy specimens from 22 patients.

BACKGROUND: Understanding whether specific histopathologic features on skin biopsy are predictive of systemic associations in dermatomyositis (DM) would be useful to guide clinical screening. METHODS: Through retrospective medical record search, clinical and laboratory findings of patients with DM were documented. Existing skin biopsy slides were re-reviewed blindly. RESULTS: Of all biopsy specimens (n = 42), the most frequent histopathological finding was vacuolar interface dermatitis (95%). Other features included perivascular lymphocytic infiltrate (71%), increased dermal mucin (40%), vessel wall thickening (12%), follicular plugging (9.5%), and dermal sclerosis (7%). Neutrophilic infiltrate was observed in three biopsies from a patient with adalimumab-associated DM. Vasculitis was not observed. There was no statistically significant difference in the presence of any histopathological feature and that of various systemic manifestations (i.e., myopathy, interstitial lung disease [ILD] and malignancy). However, we observed that dense lichenoid infiltrate rather than pauci-inflammatory changes correlated with severe itching (p < 0.001). Patients with MDA-5 antibodies were significantly more likely to have vasculopathy than those without (p = 0.029*). CONCLUSIONS: No dermatopathologic feature was reliably predictive of myopathy, ILD, or malignancy. This finding implies that, regardless of histopathologic findings, patients should be screened for associated conditions as clinically indicated.

Time to transition from psoriasis to psoriatic arthritis: A population-based study.

OBJECTIVE: To identify demographic and clinical characteristics associated with time between psoriasis and psoriatic arthritis (PsA). METHODS: A retrospective, population-based cohort of incident PsA patients ≥18 years (2000-17) from Olmsted County, MN was identified. PsA patients were divided into two groups: patients with concurrent psoriasis and PsA (within 1 year), and patients with psoriasis before PsA (>1 year). Patients with PsA prior to psoriasis were excluded. Age- and sex-adjusted logistic regression models were used to examine factors associated with the time between psoriasis and PsA diagnosis. RESULTS: Among 164 patients with incident PsA, 158 had a current or personal history of psoriasis. The mean (SD) age at PsA diagnosis was 46.3 (12.0) years, and 46% were females. The median (interquartile range) time from psoriasis to PsA was 35.5 (0.8-153.4) months. 64 patients (41%) patients had concurrent psoriasis and PsA while 94 (59%) had onset of psoriasis before PsA. The estimated age at onset of psoriasis symptom (OR per 10-year decrease = 1.63, 95% CI: 1.26-2.11) and psoriasis severity (OR = 3.65, 95% CI: 1.18-11.32 for severe vs. mild) were associated with having a psoriasis diagnosis more than one year prior to incident PsA. CONCLUSION: In this population-based study, approximately 60% of the patients had psoriasis before PsA, and the rest had concurrent psoriasis and PsA. Patients with lower age at psoriasis onset or severe psoriasis were more likely to have a longer time to transition from psoriasis to PsA.

Survival and associated comorbidities in inclusion body myositis.

OBJECTIVE: To evaluate survival and associated comorbidities in inclusion body myositis (IBM) in a population-based, case-control study. METHODS: We utilized the expanded Rochester Epidemiology Project medical records-linkage system, including 27 counties in Minnesota and Wisconsin, to identify patients with IBM, other inflammatory myopathies (IIM), and age/sex-matched population-controls. We compared the frequency of various comorbidities and survival among groups. RESULTS: We identified 50 IBM patients, 65 IIM controls and 294 population controls. Dysphagia was most common in IBM (64%) patients. The frequency of neurodegenerative disorders (dementia/parkinsonism) and solid cancers was not different between groups. Rheumatoid arthritis was the most common rheumatic disease in all groups. A total of 36% of IBM patients had a peripheral neuropathy, 6% had Sjögren's syndrome and 10% had a haematologic malignancy. T-cell large granular lymphocytic leukaemia was only observed in the IBM group. None of the IBM patients had hepatitis B or C, or HIV. IBM patients were 2.7 times more likely to have peripheral neuropathy, 6.2 times more likely to have Sjögren's syndrome and 3.9 times more likely to have a haematologic malignancy than population controls. IBM was associated with increased mortality, with a 10-year survival of 36% from index, compared with 67% in IIM and 59% in population controls. Respiratory failure or pneumonia (44%) was the most common cause of death. CONCLUSIONS: IBM is associated with lower survival, and higher frequency of peripheral neuropathy, Sjögren's syndrome and haematologic malignancies than the general population. Close monitoring of IBM-related complications is warranted.

Amyloid arthropathy in smoldering myeloma: Do not take it lightly.

We report a case of smoldering multiple myeloma patient who developed signs and symptoms consistent with polyarthritis. A PET-CT demonstrated marked FDG activity in multiple joints, concerning for inflammatory arthritis. Arthrocentesis from the glenohumeral joint was consistent with inflammatory synovial fluid with no evidence for infection or crystals. Congo-red stain of the synovial fluid was positive, and mass-spectrometry based amyloid typing was consistent with wild-type transthyretin type. The patient responded instantly to glucocorticoids. This case reports highlights the feasibility of non-tissue diagnosis of amyloidosis using body fluids and underscores the importance of accurate typing to avoid erroneous treatment.

Epidemiology and Natural History of Inclusion Body Myositis: A 40-Year Population-Based Study.

OBJECTIVES: To determine the prevalence and natural history of sporadic inclusion body myositis (sIBM) and to test the hypothesis that patients with sIBM have higher cancer or mortality rates than the general population. METHODS: We sought patients with sIBM defined by the 2011 European Neuromuscular Centre (ENMC) diagnostic criteria among Olmsted County, Minnesota, residents in 40-year time period. RESULTS: We identified 20 patients (10 clinicopathologically defined, 9 clinically defined, and 1 probable) according to the ENMC criteria and 1 patient with all features of clinicopathologically defined sIBM except for symptom onset at <45 years of age. The prevalence of sIBM in 2010 was 18.20 per 100,000 people ≥50 years old. Ten patients developed cancers. The incidence of cancers in sIBM did not differ from that observed in the general population (odds ratio 1.89, 95% confidence interval [CI] 0.639-5.613, p = 0.24). Two-thirds of patients developed dysphagia, and half required a feeding tube. Nine patients required a wheelchair. The median time from symptom onset to wheelchair dependence was 10.5 (range 1-29) years. Overall life expectancy was shorter in the sIBM group compared to the general population (84.1 [95% CI 78-88.4] vs 87.5 [95% CI 85.2-89.5] years, p = 0.03). Thirteen patients died; 9 deaths were sIBM related (7 respiratory and 2 unspecified sIBM complications). Female sex (p = 0.03) and dysphagia (p = 0.05) were independent predictors of death. CONCLUSION: Olmsted County has the highest prevalence of sIBM reported to date. Patients with sIBM have similar risk of cancer, but slightly shorter life expectancy compared to matched patients without sIBM. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that patients with sIBM have similar risks of cancers and slightly shorter life expectancy compared to controls.

The Epidemiology of Psoriatic Arthritis Over Five Decades: A Population-Based Study.

OBJECTIVE: To determine the incidence of psoriatic arthritis (PsA) in a US population and describe trends in incidence and mortality over 5 decades. METHODS: The previously identified population-based cohort that included Olmsted County, Minnesota residents ≥18 years of age who fulfilled PsA criteria during 1970-1999 was extended to include patients with incident PsA during 2000-2017. Age- and sex-specific incidence rates and point prevalence, adjusted to the 2010 US White population, were reported. RESULTS: There were 164 incident cases of PsA in 2000-2017 (mean ± SD age 46.4 ± 12.0 years; 47% female). The overall age- and sex-adjusted annual incidence of PsA per 100,000 population was 8.5 (95% confidence interval [95% CI] 7.2-9.8) and was higher in men (9.3 [95% CI 7.4-11.3]) than women (7.7 [95% CI 5.9-9.4]) in 2000-2017. Overall incidence was highest in the 40-59 years age group. The incidence rate was relatively stable during 2000-2017, with no evidence of an overall increase or an increase in men only (but a modest increase of 3% per year in women), compared to 1970-1999 when a 4%-per-year increase in incidence was observed. Point prevalence was 181.8 per 100,000 population (95% CI 156.5-207.1) in 2015. The percentage of women among those with PsA increased from 39% in 1970-1999 and 41% in 2000-2009 to 54% in 2010-2017 (P = 0.08). Overall survival in PsA did not differ from the general population (standardized mortality ratio 0.85 [95% CI 0.61-1.15]). CONCLUSION: The incidence of PsA in this predominantly White US population was stable in 2000-2017, in contrast to previous years. However, an increasing proportion of women with PsA was found in this study.

Diagnostic Delay in Psoriatic Arthritis: A Population-based Study.

OBJECTIVE: To examine demographic and clinical characteristics associated with diagnostic delay in psoriatic arthritis (PsA). METHODS: We characterized a retrospective, population-based cohort of incident adult (≥ 18 yrs) patients with PsA from Olmsted County, Minnesota, from 2000-2017. All patients met the classification criteria. Diagnostic delay was defined as the time from any patient-reported PsA-related joint symptom to a physician diagnosis of PsA. Factors associated with delay in PsA diagnosis were identified through logistic regression models. RESULTS: Of the 164 incident PsA cases from 2000 to 2017, 162 had a physician or rheumatologist diagnosis. Mean (SD) age was 41.5 (12.6) years and 46% were female. Median time from symptom onset to physician diagnosis was 2.5 years (IQR 0.5-7.3). By 6 months, 38 (23%) received a diagnosis of PsA, 56 (35%) by 1 year, and 73 (45%) by 2 years after symptom onset. No significant trend in diagnostic delay was observed over calendar time. Earlier age at onset of PsA symptoms, higher BMI, and enthesitis were associated with a diagnostic delay of > 2 years, whereas sebopsoriasis was associated with a lower likelihood of delay. CONCLUSION: In our study, more than half of PsA patients had a diagnostic delay of > 2 years, and no significant improvement in time to diagnosis was noted between 2000 and 2017. Patients with younger age at PsA symptom onset, higher BMI, or enthesitis before diagnosis were more likely to have a diagnostic delay of > 2 years, whereas patients with sebopsoriasis were less likely to have a diagnostic delay.

Erectile Dysfunction in Men With Psoriatic Arthritis: A Population-based Cohort Study.

OBJECTIVE: To define the incidence of erectile dysfunction (ED) in a population-based cohort of men with psoriatic arthritis (PsA). METHODS: Data pertaining to demographics, ED, and potential confounding diagnosis were extracted from a comprehensive medical record system for a population-based cohort of men with PsA and an age-matched male comparator cohort. Cumulative incidence of ED adjusted for competing risk of death was compared between the 2 cohorts. RESULTS: There were 128 age-matched pairs of men with PsA and without PsA in the described cohorts. At baseline, there was a 7% prevalence of ED in men with PsA prior to diagnosis compared to a 3% prevalence of ED in the comparator cohort (P = 0.16). After PsA diagnosis/index date, diagnosis with PsA was associated with an increased risk of ED (age-adjusted HR 1.45, 95% CI 0.79-2.68), but this association did not reach statistical significance. This was based on 24 cases of ED in the men with PsA and 18 cases within the comparator cohort. No confounding factors or ED treatment strategies differed significantly between men with PsA and ED and comparators with ED. CONCLUSION: Men with PsA may have an increased risk of ED, which was detected but likely underpowered in this study. Whether this difference is secondary to higher prevalence of traditional risk factors of ED in men with PsA compared to the general population will require further study.

Anti-cN1A antibodies do not correlate with specific clinical, electromyographic, or pathological findings in sporadic inclusion body myositis.

BACKGROUND: Anti-cytosolic 5'-nucleotidase 1A (cN1A) antibodies are commonly detected in patients with sporadic inclusion body myositis (sIBM). However, their pathogenic role has not been established. Moreover, efforts toward identifying sIBM distinct clinicopathologic characteristics associated with these antibodies have yielded conflicting results. METHODS: We first searched for patients, seen in our clinics, tested for anti-cN1A antibodies between December 2015 and December 2019. We identified 92 patients who were diagnosed with sIBM, according to the 2011 ENMC or Griggs et al criteria. Thereafter, we reviewed and compared the clinical and investigational findings of these patients in relation to their antibody status. RESULTS: Anti-cN1A antibodies were present in 47/92 (51%) patients with sIBM. Comparison of seropositive and seronegative cohorts yielded no significant difference in clinical features, including facial weakness, oropharyngeal and respiratory involvement, or disease severity. The antibody titer did not correlate with the clinical phenotype, CK value, or presence of myotonic discharges on EMG. Anti-cN1A antibody positive patients appeared to have more frequent auto-aggressive inflammation on muscle biopsy but not as an isolated myopathological feature. CONCLUSIONS: Our study showed that anti-cN1A antibody positive and negative sIBM patients have similar clinical features and disease severity. Anti-cN1A antibodies in our sIBM cohort did not correlate with any studied clinical or laboratory parameter and, therefore, were of limited value in the patient's assessment.

Proteinase 3 (PR3)-antineutrophil cytoplasmic antibody (ANCA)-associated vasculitic neuropathy in diffuse cutaneous systemic sclerosis: a rare duo.

Systemic sclerosis (SSc) is characterised by non-inflammatory vasculopathy, autoimmunity and widespread fibrosis. While the presence of antineutrophil cytoplasmic antibodies (ANCAs) has been reported in SSc, their association with ANCA-associated vasculitis is exceedingly rare. Myeloperoxidase ANCA is more common than proteinase-3 ANCA, and glomerulonephritis is the most common clinical presentation of ANCA-associated vasculitis in SSc. ANCAs have been associated with the adverse disease outcomes in SSc, including higher mortality per recent reports. A 65-year-old man with diffuse cutaneous SSc for 6 years presented with new-onset peripheral neuropathy. Workup revealed a positive proteinase-3 and cytoplasmic ANCA, and histopathology confirmed an inflammatory vasculitic neuropathy. The patient was successfully treated with rituximab. Our case highlights the importance of checking ANCA in SSc at baseline, given the risk of disease-related complications, even years later. Tissue biopsy is often warranted for confirmation of vasculitis and prompt treatment can optimise long-term outcomes.

Anti-HMGCR myopathy presenting with acute systolic heart failure.

Necrotising autoimmune myopathy (NAM) is an immune-mediated myopathy that may be associated with statin use, malignancy or an autoimmune connective tissue disease, but it can also be idiopathic. Anti-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) myopathy is an extremely rare side effect of statin use, occurring in approximately 2-3 out of every 100 000 patients who use statins. Patients typically present with subacute proximal muscle weakness and creatine kinase levels >10 times the upper limit of normal. The diagnosis is suggested by muscle biopsy showing necrotic fibres with minimal inflammation along with positive anti-HMGCR antibodies. Treatment nearly always requires multiple immunosuppressive agents, the earlier use of which is associated with improved outcomes. Reports of statin-induced NAM leading to heart failure are limited. We present the case of a 69-year-old woman with statin-induced NAM who presented with acute systolic heart failure. Early initiation of high-dose corticosteroids and IVIG resulted in significant improvement in her symptoms.

Lupus-Associated Functional Polymorphism in PNP Causes Cell Cycle Abnormalities and Interferon Pathway Activation in Human Immune Cells.

OBJECTIVE: Systemic lupus erythematosus (SLE) is frequently characterized by activation of the type I interferon (IFN) pathway. We previously observed that a missense single-nucleotide polymorphism (rs1049564) in the purine nucleoside phosphorylase (PNP) gene was associated with high levels of IFN in SLE. PNP is a key enzyme involved in purine metabolism. In this study, we performed functional follow-up of this polymorphism in human cells. METHODS: Type I IFN was measured in patient sera, using a reporter cell assay. Structural modeling of the PNP variant was performed using PyMOL software. PNP messenger RNA (mRNA) and protein levels and type I IFN-induced gene expression were measured in lymphoblastoid cell lines with known PNP rs1049564 genotypes. The cell cycle was assayed using flow cytometry. RESULTS: Structural modeling indicated no major disruption in folding related to rs1049564. We observed that homozygous rs1049564 TT lymphoblastoid cells had decreased PNP mRNA expression and protein levels, and that cells with the TT genotype had reduced PNP enzymatic activity even when the amount of PNP was controlled. Cells with the TT genotype had a 2-fold increase in S-phase block as compared with cells with the homozygous CC phenotype. The S-phase block could be pharmacologically reversed with hypoxanthine and adenosine, supporting the notion that relative PNP deficiency is the cause of the S-phase block. Type I IFN-induced transcripts were increased in a dose-response manner related to the rs1049564 T allele, at both baseline and after type I IFN stimulation. CONCLUSION: The PNP rs1049564 T allele is a loss-of-function variant that induces S-phase block and IFN pathway activation in lymphocytes. The S-phase block could be rescued in our in vitro experiments, suggesting the potential for personalized treatment.

Residency Training: Quality improvement projects in neurology residency and fellowship: applying DMAIC methodology.

OBJECTIVE: Teaching quality improvement (QI) is a priority for residency and fellowship training programs. However, many medical trainees have had little exposure to QI methods. The purpose of this study is to review a rigorous and simple QI methodology (define, measure, analyze, improve, and control [DMAIC]) and demonstrate its use in a fellow-driven QI project aimed at reducing the number of delayed and canceled muscle biopsies at our institution. METHODS: DMAIC was utilized. The project aim was to reduce the number of delayed muscle biopsies to 10% or less within 24 months. Baseline data were collected for 12 months. These data were analyzed to identify root causes for muscle biopsy delays and cancellations. Interventions were developed to address the most common root causes. Performance was then remeasured for 9 months. RESULTS: Baseline data were collected on 97 of 120 muscle biopsies during 2013. Twenty biopsies (20.6%) were delayed. The most common causes were scheduling too many tests on the same day and lack of fasting. Interventions aimed at patient education and biopsy scheduling were implemented. The effect was to reduce the number of delayed biopsies to 6.6% (6/91) over the next 9 months. CONCLUSIONS: Familiarity with QI methodologies such as DMAIC is helpful to ensure valid results and conclusions. Utilizing DMAIC, we were able to implement simple changes and significantly reduce the number of delayed muscle biopsies at our institution.

Cancer risk in dermatomyositis: a meta-analysis of cohort studies.

BACKGROUND: An association between dermatomyositis (DM) and cancer has been reported since 1916; however, estimates of the associated risk vary widely. For cost-effectiveness reasons it might be important to elucidate the degree of overall cancer risk in DM. OBJECTIVE: The aim of this systematic review was to investigate the association of cancer in DM by performing a meta-analysis of cohort studies. DATA SOURCES: A systematic literature search of PubMed, Ovid MEDLINE, EMBASE, Web of Science, Scopus, and the Cochrane Collaboration was conducted without language restriction, to 1 May 2014. STUDY SELECTION: Inclusion criteria included cohort studies assessing overall cancer risk in DM. Two reviewers independently performed the study selection. Inter-rater reliability for inclusion decisions was quantified using Cohen's κ statistic. Disagreements were resolved by discussion. DATA EXTRACTION AND SYNTHESIS: Desired variables were extracted from eligible studies independently by two investigators and disagreements were resolved by discussion. Quality of the selected studies was assessed using a modification of a recently employed system designed with reference to Meta-analysis Of Observational Studies in Epidemiology (MOOSE), Quality Assessment Tool for Systematic Reviews of Observational Studies (QATSO), and Strengthening the Reporting of Observational Studies in Epidemiology (STROBE). Summary estimates were derived using a random-effects model. MAIN OUTCOME(S) AND MEASURE(S): Main outcome was the calculated relative risk of developing cancer after diagnosis of DM compared with the general population, estimated as the age- and sex-adjusted standardized incidence ratio (SIR). We hypothesized a priori that the relative risk would be higher in patients diagnosed with DM. RESULTS: A total of 1,272 articles were initially identified but only ten studies met the inclusion criteria. Selected studies included seven population-based and three hospital-based DM cohorts that ranged from 49 to 1,012 patients and had mean follow-up times from 3.7 to 10.4 years. The pooled SIR for the incidence of overall cancer in DM patients was 4.79 (95% confidence interval 3.71-5.87) with significant heterogeneity (I(2) = 85.8%). However, the heterogeneity had no substantial influence on the pooled SIR for overall cancer in DM according to the sensitivity analysis. CONCLUSIONS: Compared with the general population, DM patients are at a significantly increased risk for developing cancer. Understanding the magnitude of this risk is highly relevant toward assisting healthcare providers in clinical decision making, such as screening DM patients for cancer.

Frequency and spectrum of myopathies in patients with psoriasis.

INTRODUCTION: Psoriasis is a T-cell-mediated skin disorder with uncommon extracutaneous manifestations. Rare patients with psoriasis and myopathy have been reported. METHODS: We conducted a retrospective review of medical records of psoriasis patients seen at the Mayo Clinic during the period from January 1, 1996 to May 31, 2011. Patients who had pathologically confirmed myopathy or lymphocytic infiltrates in muscle were included. RESULTS: Among 11,370 psoriasis patients, 13 had pathologically confirmed myopathies. Seventy percent were inflammatory myopathies, and 2 had focal inflammation in the muscle. Psoriasis preceded myopathy onset in two-thirds of the patients (median 14.7 years). Half of the patients had psoriatic arthritis; 60% had other autoimmune disorders. Patients who received anti-tumor necrosis factor-alpha (anti-TNF-α) therapy had a higher risk for developing myopathy or inflammation in muscle (odds ratio = 4.45). CONCLUSIONS: Myopathy or inflammation in muscle affects an average of 1.32 of every 1000 psoriasis patients. Concomitant autoimmune disorders, psoriatic arthritis, and exposure to anti-TNF-α therapy may be associated with increased risk of developing myopathy in psoriasis patients.

Idiopathic inflammatory myopathies: current trends in pathogenesis, clinical features, and up-to-date treatment recommendations.

Recently, there have been important advances in the understanding of the pathophysiologic features, assessment, and management of patients with a newly diagnosed idiopathic inflammatory myopathy (IIM). Myositis-specific autoantibodies have been identified to define patient subgroups and offer prognostic implications. Similarly, proinflammatory cytokines, such as interleukin 6 and type 1 interferon-dependent genes, may serve as potential biomarkers of disease activity in adult and juvenile patients with dermatomyositis (DM). Moreover, magnetic resonance imaging has become an important modality for the assessment of muscle inflammation in adult IIM and juvenile DM. Immune-mediated necrotizing myopathies also are being recognized as a subset of IIM triggered by medications such as statins. However, confusion exists regarding effective management strategies for patients with IIM because of the lack of large-scale, randomized, controlled studies. This review focuses primarily on our current management and treatment algorithms for IIM including the care of pediatric patients with juvenile DM. For this review, we conducted a search of PubMed and MEDLINE for articles published from January 1, 1970, to December 1, 2011, using the following search terms: idiopathic inflammatory myopathies, dermatomyositis, polymyositis, juvenile dermatomyositis, sporadic inclusion body myositis, inclusion body myositis, inflammatory myositis, myositis, myopathies, pathogenesis, therapy, and treatment. Studies published in English were selected for inclusion in our review as well as additional articles identified from bibliographies.

Changes in novel biomarkers of disease activity in juvenile and adult dermatomyositis are sensitive biomarkers of disease course.

OBJECTIVE: Muscle enzyme levels are insensitive markers of disease activity in juvenile and adult dermatomyositis (DM), especially during the active treatment phase. To improve our ability to monitor DM disease activity longitudinally, especially in the presence of immunomodulating agents, we prospectively evaluated whether interferon (IFN)-dependent peripheral blood gene and chemokine signatures could serve as sensitive and responsive biomarkers for change in disease activity in adult and juvenile DM. METHODS: Peripheral blood and clinical data were collected from 51 patients with juvenile or adult DM prospectively over 2 study visits. We performed disease activity measurements and calculated whole-blood type I IFN gene and chemokine scores. We also measured serum levels of other proinflammatory cytokines, including interleukin-6 (IL-6). RESULTS: Changes in juvenile and adult DM global disease activity correlated positively and significantly with changes in the type I IFN gene score before adjustment for medication use (r = 0.33, P = 0.023) and with changes in the IFN chemokine score before and after adjustment for medication use (r = 0.53, P < 0.001 and r = 0.50, P < 0.001, respectively). Changes in muscle and extramuscular visual analog scale (VAS) scores correlated positively with changes in IFN gene and chemokine scores (P = 0.002, P < 0.001, P = 0.095, P < 0.001). Serum levels of IL-6, IL-8, and tumor necrosis factor α (TNFα) correlated positively with changes in global, muscle, and extramuscular VAS scores (P < 0.05). CONCLUSION: Our findings suggest that changes in type I IFN gene and chemokine scores as well as in levels of IL-6, IL-8, and TNFα may serve as sensitive and responsive longitudinal biomarkers of change in disease activity in juvenile and adult DM, even in the presence of immunomodulating agents.

The inflammatory milieu in idiopathic inflammatory myositis.

The idiopathic inflammatory myopathies (IIM) are systemic autoimmune diseases that have predominant mononuclear inflammatory cell infiltrates in the skeletal muscle. The cells that are typically involved in the pathogenesis of disease are B-lymphocytes, T-lymphocytes, macrophages, dendritic cells, and natural killer cells. However, in addition to these immune cells, cells of nonimmunologic origin, such as myocytes, may be directly involved in the immune response. The local milieu also consists of distinct cytokine and chemokine profiles considered related to type 1 interferon stimulation. Tumor necrosis factor and interleukin 1 are also prominent, proinflammatory cytokines involved in the evolution of IIM. Although the pathologic processes involved in IIM have yet to be fully elucidated, we understand the inflammatory milieu is a model of dynamic flux made of diverse cytokine and chemokine expressions leading to alterations in muscle fiber structure and function.