tacrolimus and Polymyositis

To evaluate the efficacy and safety of tacrolimus for dermatomyositis (DM) and polymyositis (PM) treatment.. We searched the Embase, PubMed, the Cochrane Central Register of Controlled Trials, and China National Knowledge Infrastructure were used as searching tools from inception up to October 2022. Two authors independently selected studies. The available studies were comprehensively reviewed and investigated.. A total of 9 studies, including 350 patients, were analysed. Pooled results showed a higher overall survival rate in tacrolimus therapy group. Creatine kinase (CK) levels and forced vital capacity (FVC) showed significant improvement after tacrolimus therapy. The incidence of adverse events including infection and renal dysfunction showed no significant differences between the tacrolimus therapy group and conventional therapy group.. The results of this meta-analysis indicated that GC therapy in combination with tacrolimus therapy could help improving overall survival rate, pulmonary function and had similar safety outcomes compared to conventional therapy in DM and PM patients.

Topics: Dermatomyositis; Drug Therapy, Combination; Humans; Immunosuppressive Agents; Polymyositis; Tacrolimus

The purpose of this study is to examine the efficacy and safety of tacrolimus (FK506) in the management of polymyositis (PM)/dermatomyositis (DM). The Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, and China National Knowledge Infrastructure (CNKI) were searched to find articles published between May 1980 and April 2015 concerning tacrolimus therapy in PM/DM. The initial search yielded 107 articles. In the end, eight studies met our inclusion criteria and involved a total of 134 patients who received tacrolimus therapy for DM/PM. All studies were non-randomized. Oral tacrolimus of 0.075 mg/kg/day or 1.0-3.5 mg/d was administered twice daily or once daily together with glucocorticoids (GCs). According to comprehensive analysis of the studies, 93.3 % (42/45) and 64.7 % (11/17) of patients showed improvement in muscle strength and physical function status. The creatine kinase (CK) levels of 100 % (68/68) of patients decreased. The average dosage of GCs was reduced from 33.8 to 11.5 mg/day in PM/DM patients after the addition of tacrolimus. In the subject population, 65 patients had interstitial lung disease (ILD). After treatment, the forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO) improved or stabilized in 89.3 % (25/28) and 81.3 % (13/16) of patients, respectively. The commonly adverse events were nephrotoxicity, hypomagnesemia, tremors, and hypertension, but they were slight among these patients. Current evidence appears to support the use of tacrolimus in refractory PM/DM and PM/DM-ILD patients. Tacrolimus seems to be a safe drug that improves both muscle strength and lung function, and it is well tolerated by patients. However, this conclusion should be confirmed by large-sample, randomized controlled studies.

Topics: Dermatomyositis; Drug Therapy, Combination; Glucocorticoids; Humans; Immunosuppressive Agents; Lung Diseases, Interstitial; Polymyositis; Tacrolimus; Treatment Outcome

Dermatomyositis (DM) and polymyositis (PM) are often refractory to conventional therapy with corticosteroids sometimes combined with immune-suppressing agents and can lead to severe disability if these treatments are unsuccessful. In this prospective, open, non-randomized study, we examined the efficacy of tacrolimus (FK506), an immunosuppressant, in nine patients with DM (n = 5) or PM (n = 4) who did not respond to previous therapy. Outcomes included compound muscle strength, ambulatory status, and serum creatine kinase activity measured at intervals after starting tacrolimus. At 6 months after the introduction of tacrolimus, all five patients with DM and three patients with PM showed clinical improvements. Patients with a disease duration of <4 years and those with trough level of tacrolimus >5 ng/ml tended to have better outcomes than those with longer disease duration or lower trough levels. There were no side effects other than moderate hypertension and aggravation of diabetes mellitus. Tacrolimus was beneficial in the majority of patients with PM or DM refractory to corticosteroid therapy. It was also effective in four patients who were previously treated with other immunosuppressants or intravenous immunoglobulin combined with corticosteroids. These results warrant further studies as to the efficacy of tacrolimus compared to other immunosuppressing agents.

Topics: Adult; Aged; Creatine Kinase; Dermatomyositis; Dose-Response Relationship, Drug; Female; Humans; Immunosuppressive Agents; Longitudinal Studies; Male; Middle Aged; Muscle Strength; Polymyositis; Prospective Studies; Tacrolimus; Treatment Outcome

To review the treatment advances of the inflammatory myopathies, a heterogeneous group of diseases that includes polymyositis, dermatomyositis, and inclusion body myositis.. There are few clinical trials in myositis, making it difficult to provide clear recommendations on the treatment of these rare disorders. The current management for IIM includes the initial use of corticosteroids followed by various conventional second-line treatments such as methotrexate and azathioprine. Although these drugs have not been tested in rigorous randomized controlled trials, general expert consensus confirms their use. Intravenous immunoglobulin is a reasonable short-term treatment with proven benefit in one controlled trial, although the evidence for other immunosuppressive therapies has been derived mainly from uncontrolled studies. Cyclosporine or tacrolimus have shown efficacy in myositis including those patients with interstitial lung disease (ILD), whereas mycophenolate mofetil is effective in both polymyositis and refractory dermatomyosits (including recalcitrant rash) and ILD. Uncontrolled studies for rituximab are encouraging but results from the largest randomized controlled trial in myositis failed to meet the primary endpoint. Anti-tumor necrosis factor (TNF) agents have shown mixed results in small, randomized clinical trials with infliximab demonstrating no benefit and etanercept leading to encouraging results warranting further study. Some newer novel therapies such as ACTH analogues and tocilizumab require additional investigation.. The balance of evidence suggests that traditional immunosuppressive and immunomodulatory drugs are certainly effective in polymyositis and dermatomyositis despite the lack of randomized controlled trials. Newer therapies are being studied but no major breakthroughs have been realized.

Topics: Azathioprine; Cyclosporine; Dermatomyositis; Drug Resistance; Drug Therapy, Combination; Glucocorticoids; Humans; Immunoglobulins, Intravenous; Immunomodulation; Immunosuppressive Agents; Methotrexate; Mycophenolic Acid; Polymyositis; Randomized Controlled Trials as Topic; Tacrolimus

Inflammatory myopathies are chronic, immune-mediated diseases characterized with progressive proximal muscle weakness. They encompass a variety of syndromes with protean manifestations. The aims of therapy are to increase muscle strength, prevent the development of contractures, and to manage the systemic manifestations of the disease. This is a complex treatment which requires routine and wide knowledge. The most important task is to recognize the disease and guide the patient to immunologic center. Although the first line of therapy continues to include corticosteroids, there are a multitude of agents available for treating patients with myositis. There are several different immunosuppressive agents which may be applied alone or in combination with each other, as well as an increasing number of novel and exciting biologic agents targeting molecules participating in the pathogenesis of inflammatory myopathy. Physiotherapy and rehabilitation in the remission period may significantly improve the functional outcome of patients with these disorders.

Topics: Adrenal Cortex Hormones; Algorithms; Antineoplastic Agents; Azathioprine; Biological Therapy; Cell Movement; Cyclophosphamide; Cyclosporine; Dermatomyositis; Exercise Therapy; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Methotrexate; Mycophenolic Acid; Paraneoplastic Syndromes; Physical Therapy Modalities; Polymyositis; T-Lymphocytes; Tacrolimus

Graft-versus-host disease (GVHD) remains a major complication of allogeneic hematopoietic stem cell transplantation. Polymyositis can occur in association with chronic GVHD and mimics the idiopathic form of the disease. We report two cases of chronic GVHD-associated polymyositis and review the published literature. The two patients presented 13 and 19 months after allogeneic transplantation with characteristic features of muscular hypotrophy, proximal muscle weakness, pain, elevated creatine phosphokinase (CPK), aldolase and SGPT. Interestingly, both patients had HLA DR52 genes, which is frequently reported in association with idiopathic polymyositis. Electromyogram (EMG) and muscle biopsy confirmed the diagnosis. Treatment with cyclosporine or tacrolimus resulted in complete and sustained remission of polymyositis in both cases. A review of the literature shows cyclosporine and steroids are well-described treatment options for patients with myositis in post transplant, as well as idiopathic cases. The duration of immunosuppressive treatment has varied in different reports, and there is a risk of recurrence when immunosuppression is tapered.

Topics: Adult; Chronic Disease; Cyclosporine; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid; Male; Middle Aged; Polymyositis; Tacrolimus; Transplantation, Homologous

It is well known that a certain percentage of patients with polymyositis and dermatomyositis (PM/DM) is corticosteroid resistant. Established and novel approaches to steroid-resistant PM/DM are discussed in this review. Methotrexate (MTX) is a first-line treatment in the case that steroid therapy fails. Azathioprine and cyclophosphamide also fall into this category. Cyclosporine, a specific inhibitor of calcineurin, has been reported almost as effective as MTX. Tacrolimus, also a calcineurin inhibitor, and mycophenolate mofetil could be additional alternatives for the treatment. Several clinical trials have demonstrated that high-dose intravenous immunoglobulin is promising. Recently favorable data have been published using intravenous high-dose pulse cyclophosphamide or cyclosporine for the poorly prognostic interstitial pneumonitis or pulmonary fibrosis accompanied with PM/DM.

Topics: Animals; Anti-Inflammatory Agents; Azathioprine; Cyclophosphamide; Cyclosporine; Dermatomyositis; Drug Resistance; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Lung Diseases, Interstitial; Methotrexate; Mycophenolic Acid; Polymyositis; Steroids; Tacrolimus

Evaluation of new therapies for the inflammatory myopathies is complicated by the heterogeneity of these syndromes as well as by the lack of internationally accepted definitions of disease categories and assessments of disease activity and chronicity. This review covers our opinion of therapies and emphasizes the need for an early rehabilitation evaluation for these patients. Oral corticosteroids are the first line of therapy for the inflammatory myopathies, but because of their side effects and the existence of a subset of patients in whom disease is controlled only with high-dose corticosteroids, we recommend considering the early use of a second-line immunomodulating agents or pulse intravenous methylprednisolone. A stepwise progression of therapies is suggested for patients who have increasing muscle weakness resulting from active disease.

Topics: Azathioprine; Chlorambucil; Cyclophosphamide; Cyclosporine; Dermatomyositis; Drug Therapy, Combination; Glucocorticoids; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Methotrexate; Methylprednisolone; Polymyositis; Tacrolimus

Interstitial pneumonia is common and has high short-term mortality in patients with PM and DM despite glucocorticoid (GC) treatment. Retrospective studies suggested that the early use of immunosuppressive drugs with GCs might improve its short-term mortality.. A multicentre, single-arm, 52-week-long clinical trial was performed to test whether the initial combination treatment with tacrolimus (0.075 mg/kg/day, adjusted for the target whole-blood trough levels between 5 and 10 ng/ml) and GCs (0.6-1.0 mg/kg/day of prednisolone followed by a slow taper) improves short-term mortality of PM/DM-interstitial pneumonia patients. The primary outcome was overall survival. We originally intended to compare, by using propensity-score matching, the outcome data of clinical trial patients with that of historical control patients who were initially treated with GCs alone.. The 52-week survival rate with the combination treatment (N = 26) was 88.0% (95% CI, 67.3, 96.0). Safety profiles of the combination treatment were consistent with those known for tacrolimus and high-dose GCs individually. Serious adverse events occurred in 11 patients (44.0%), which included four opportunistic infections. Only 16 patients, including only 1 deceased patient, were registered as historical controls, which precluded meaningful comparative analysis against the clinical trial patients.. Our study provided findings which suggest that initial treatment with tacrolimus and GCs may improve short-term mortality of PM/DM-interstitial pneumonia patients with manageable safety profiles. This was the first prospective clinical investigation conducted according to the Good Clinical Practice Guideline of the International Conference on Harmonization for the treatment of this potentially life-threatening disease.. ClinicalTrials.gov, http://clinicaltrials.gov, NCT00504348.

Topics: Adult; Aged; Cause of Death; Comorbidity; Dermatomyositis; Disease-Free Survival; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Japan; Kaplan-Meier Estimate; Lung Diseases, Interstitial; Male; Middle Aged; Outcome Assessment, Health Care; Polymyositis; Prospective Studies; Respiratory Function Tests; Risk Assessment; Survival Rate; Tacrolimus

Dermatomyositis (DM) and polymyositis (PM) are often refractory to conventional therapy with corticosteroids sometimes combined with immune-suppressing agents and can lead to severe disability if these treatments are unsuccessful. In this prospective, open, non-randomized study, we examined the efficacy of tacrolimus (FK506), an immunosuppressant, in nine patients with DM (n = 5) or PM (n = 4) who did not respond to previous therapy. Outcomes included compound muscle strength, ambulatory status, and serum creatine kinase activity measured at intervals after starting tacrolimus. At 6 months after the introduction of tacrolimus, all five patients with DM and three patients with PM showed clinical improvements. Patients with a disease duration of <4 years and those with trough level of tacrolimus >5 ng/ml tended to have better outcomes than those with longer disease duration or lower trough levels. There were no side effects other than moderate hypertension and aggravation of diabetes mellitus. Tacrolimus was beneficial in the majority of patients with PM or DM refractory to corticosteroid therapy. It was also effective in four patients who were previously treated with other immunosuppressants or intravenous immunoglobulin combined with corticosteroids. These results warrant further studies as to the efficacy of tacrolimus compared to other immunosuppressing agents.

Topics: Adult; Aged; Creatine Kinase; Dermatomyositis; Dose-Response Relationship, Drug; Female; Humans; Immunosuppressive Agents; Longitudinal Studies; Male; Middle Aged; Muscle Strength; Polymyositis; Prospective Studies; Tacrolimus; Treatment Outcome

The calcineurin inhibitor tacrolimus has been approved in Japan for the treatment of interstitial pneumonia (IP) in patients with polymyositis (PM) and dermatomyositis (DM). Postmarketing surveillance was initiated to examine long-term outcomes of immunosuppressive regimens containing tacrolimus in real-world settings.. Observational, prospective, postmarketing surveillance is ongoing in 179 patients with PM/DM-associated IP initiating treatment with tacrolimus. We report interim findings after 2 years of follow-up. Cumulative overall survival was assessed using Kaplan-Meier analysis. Potential prognostic factors for mortality were assessed by univariate Cox proportional hazards analysis.. A total of 170 patients were included in this analysis. At the time of starting treatment with tacrolimus, almost all patients were receiving corticosteroids (98.8%), and cyclophosphamide was additionally used in 42 patients (24.7%). Forty-nine patients (28.8%) discontinued tacrolimus during follow-up, mainly due to loss to follow-up, patient death, and adverse events. Mean (SD) oral corticosteroid dose decreased from 32.4 (21.6) mg/day at baseline to 7.6 (4.2) mg/day at 2 years. Overall survival at 2 years was 90.3%; corresponding progression-free survival was 62.5%. Factors found to be associated with all-cause mortality included diagnosis of clinically amyopathic DM (hazard ratio [HR] 9.04, 95% CI 1.18-69.51 vs PM), ferritin level 500 to < 1500 ng/mL (HR 8.61, 95% CI 2.51-29.45 vs < 500 ng/mL), and presence of antimelanoma differentiation-associated gene 5 antibodies (HR 8.16, 95% CI 1.03-64.47 vs absence).. Immunosuppressive regimens containing tacrolimus appear useful for the management of IP in patients with PM/DM. [ClinicalTrials.gov: NCT02159651].

Topics: Adrenal Cortex Hormones; Dermatomyositis; Humans; Immunosuppressive Agents; Japan; Lung Diseases, Interstitial; Polymyositis; Prospective Studies; Retrospective Studies; Tacrolimus

  A 65-year-old woman with a 17-year history of polymyositis and 8-year history of rheumatoid arthritis who was treated with a low dose of prednisolone and tacrolimus (Tac) was admitted to our hospital because of general malaise and hypertension. Blood tests showed thrombocytopenia, hemolytic anemia with fragmented erythrocytes, and hypercreatinemia. Based on these clinical features, she was diagnosed with thrombotic micro-angiopathy (TMA). Thrombocytopenia and hemolytic anemia with fragmented erythrocytes improved with the discontinuation of Tac and plasma exchange; however, hypertension and renal dysfunction persisted. TMA due to calcineurin inhibitor (CNI) nephropathy was suspected based on the histopathological findings of renal biopsy. However, the condition was atypical of a CNI nephropathy because the trough level of Tac was lower than that reported previously and renal dysfunction persisted after drug discontinuation. She had mild sclerodactylia and Raynaud's symptoms, although the diagnostic criteria for systemic sclerosis (SSc) were not satisfied. Moreover, the patient tested positive for anti PL-7 antibody. The relationship between anti PL-7 antibody and pathogenesis of SSc has been reported. In this case, it was suspected that CNI nephropathy worsened because of the potential basic factors of SSc. These findings indicate that TMA may occur in patients testing positive for anti PL-7 antibody who are treated with Tac.

Topics: Aged; Amino Acyl-tRNA Synthetases; Arthritis, Rheumatoid; Autoantibodies; Biomarkers; Calcineurin Inhibitors; Female; Humans; Plasma Exchange; Polymyositis; Tacrolimus; Thrombotic Microangiopathies; Withholding Treatment

Topics: Azathioprine; Drug Substitution; Drug Therapy, Combination; Gynecomastia; Humans; Immunosuppressive Agents; Lung Diseases, Interstitial; Male; Methylprednisolone; Middle Aged; Polymyositis; Prednisone; Tacrolimus

Polymyositis (PM) is an inflammatory muscle disease characterized by chronic inflammation in skeletal muscle. Although most patients with PM respond to corticosteroids, some cases show an unsatisfactory response and other therapeutic options must be considered. Furthermore, glucocorticosteroid (GC) toxicity leads to a significant disability known as steroid myopathy, particularly in elderly patients. Here we report two patients with refractory PM. Combined treatment with high-dose GCs, tacrolimus, and intravenous immunoglobulin resulted in beneficial effects against myositis. However, muscle weakness and the disability progressed due to steroid myopathy, and subsequent oral intake became impossible because of swallowing disturbance in these two patients. Nutritional intervention, including branched-chain amino acids (BCAAs) and rehabilitation, was undertaken in addition to treatment against myositis. These treatments finally improved the muscle weakness and activities of daily living, and the two patients were discharged after recovery. The high-dose GC treatment caused elevation of serum levels of amino acids, including BCAAs, but these amino acids subsequently declined during BCAA replacement therapy. These findings suggest that the catabolic effects of the glucocorticoid treatment impair the balance of amino acids, including BCAAs, within the muscle, leading to steroid myopathy.

Topics: Female; Glucocorticoids; Humans; Immunoglobulins, Intravenous; Middle Aged; Muscle Weakness; Muscle, Skeletal; Polymyositis; Tacrolimus; Treatment Outcome

Interstitial lung diseases (ILDs) complicated with PM or DM are frequently aggressive and refractory to treatment. Recently some reports have suggested the potential benefit of tacrolimus for severe ILD complicated with PM/DM. However, little evidence has yet shown the efficacy of tacrolimus in these settings. The aim of this study was to evaluate the efficacy of tacrolimus as a treatment for PM-/DM-related ILD.. This retrospective study comprised 49 previously untreated patients diagnosed as PM-/DM-related ILD admitted to Hokkaido University Hospital from January 2000 to July 2013. These patients were treated with tacrolimus plus conventional therapy or only with conventional therapy (prednisolone, i.v. CYC and/or ciclosporin). The primary endpoint was defined as the time to relapse or death of respiratory cause or a serious adverse event. The secondary endpoint was defined as the time from the initiation of immunosuppressive treatment to relapse or death of respiratory cause. Endpoints were compared by adjusted Cox regression model by using inverse probability of treatment weighting in order to reduce the impact of these selection biases and potential confounding factors.. After adjustment, the tacrolimus group (n = 25) had significantly longer event-free survival as compared with the conventional therapy group (n = 24). The weighted hazard ratio (HR) was 0.32 (95% CI 0.14, 0.75, P = 0.008). In addition, the tacrolimus group had significantly longer disease-free survival as compared with the conventional therapy group. The weighted HR was 0.25 (95% CI 0.10, 0.66, P = 0.005).. The addition of tacrolimus to conventional therapy significantly improved the prognosis of patients with PM-/DM-related ILD.

Topics: Adult; Aged; Dermatomyositis; Endpoint Determination; Female; Humans; Immunosuppressive Agents; Japan; Lung Diseases, Interstitial; Male; Middle Aged; Polymyositis; Prognosis; Proportional Hazards Models; Retrospective Studies; Survival Rate; Tacrolimus; Treatment Outcome

Topics: Dermatomyositis; Female; Humans; Immunosuppressive Agents; Lung Diseases, Interstitial; Male; Polymyositis; Tacrolimus

In the treatment of polymyositis (PM) and dermatomyositis (DM), muscle inflammation and underlying autoimmunity need to be suppressed promptly; however, catabolic effects of corticosteroids such as myopathy can be detrimental in PM/DM. In this study, we aimed to assess the corticosteroid-sparing effect of tacrolimus in the initial treatment of PM/DM.. We retrospectively identified 19 PM/DM patients who received initial treatment with prednisolone at an initial dose of 1 mg/kg/day (Conventional Monotherapy, our standard therapy before 2008) and 23 patients with tacrolimus plus prednisolone at an initial dose 0.8 mg/kg/day (Tacrolimus Combination, our standard therapy after 2008). Data until 36 months after commencing treatment were collected.. There were no statistically significant differences in baseline characteristics between two groups. Median daily dose of prednisolone in the Tacrolimus Combination Group was significantly lower than that in the Conventional Monotherapy Group during the study period, whereas the proportion of patients who required additional immunosuppressive medications for remission induction was comparable. Remission was achieved in all patients, except one who died of refractory interstitial lung disease after receiving Conventional Monotherapy. The time required for creatine kinase normalization and relapse rate was comparable between two groups. The period of hospitalization for initial treatment was significantly shorter and survival without serious infection or relapse tended to be longer in the Tacrolimus Combination than the Conventional Monotherapy.. This study provides real-life data which demonstrate that tacrolimus has a corticosteroid-sparing effect and reduces the length of hospitalization period for the initial treatment of PM/DM.

Topics: Adrenal Cortex Hormones; Adult; Dermatomyositis; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Length of Stay; Male; Middle Aged; Myositis; Polymyositis; Prednisolone; Retrospective Studies; Tacrolimus

Topics: Dermatomyositis; Female; Humans; Immunosuppressive Agents; Lung Diseases, Interstitial; Male; Polymyositis; Tacrolimus

Topics: Dermatomyositis; Female; Humans; Immunosuppressive Agents; Lung Diseases, Interstitial; Male; Polymyositis; Tacrolimus

Tacrolimus, also known as FK506, is an immunosuppressive agent widely used for the prevention of acute allograft rejection in organ transplantation and for the treatment of immunological diseases. This study reports two male patients who underwent solid organ transplantation (liver and kidney). After transplant, the patients received continuous immunosuppressive therapy with oral tacrolimus and later presented clinical manifestations and laboratory signs of myopathy. Muscle biopsies of both patients clearly documented an inflammatory myopathy with the histological features of polymyositis including CD8+ T cells which invaded healthy muscle fibers and expressed granzyme B and perforin, many CD68+ macrophages and MHC class I antigen upregulation on the surface of most fibers. Because of the temporal association while receiving tacrolimus and since other possible causes for myopathy were excluded, the most likely cause of polymyositis in our patients was tacrolimus toxicity. We suggest that patients on tacrolimus should be carefully monitored for serum CK levels and clinical signs of muscle disease.

Topics: ADP-ribosyl Cyclase 1; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Biopsy; Humans; Immunosuppressive Agents; Male; Middle Aged; Muscles; Organ Transplantation; Polymyositis; Tacrolimus

We performed an observational clinical study, the effects of tacrolimus (FK506) on the thymic output in patients with refractory inflammatory myopathies. Sixteen patients with polymyositis (PM) and 15 with dermatomyositis (DM) were treated orally with tacrolimus. Serum CK levels significantly decreased 2 to 4 months after tacrolimus therapy (p < 0.01), and MRC (Medical Research Council) scores were significantly improved 2 months after tacrolimus therapy (p < 0.01). T-cell receptor excision circle (TREC) content, a proxy for thymic export was not significantly different from that in age-matched controls, except for an increase in the TREC content within CD8+ single positive cells in patients with DM. TREC contents within double-positive cells and CD4+ single-positive cells were significantly decreased 4 M after tacrolimus therapy (p < 0.05) in PM/DM patients. Tacrolimus treatment significantly attenuated TREC content within cultured CD4+CD8- cells from PM/DMpatients (p < 0.05), but total cell counts were not significantly changed. These results indicate that tacrolimus therapy suppresses not only activated T-lymphocytes, but also some naïve T-cell subsets in both PM and DM.

Topics: Administration, Oral; Aged; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cells, Cultured; Dermatomyositis; Humans; Immunosuppressive Agents; Lymphocyte Activation; Middle Aged; Polymyositis; Tacrolimus

A 30-year-old pregnant woman experienced mild dyspnea in April 2009. She complained of mild myalgia and was subsequently admitted to our hospital in June 2009 because of worsening dyspnea. Physical examination revealed fine crackles in the lower lung field, but no eruptions externally. Laboratory findings revealed elevated serum levels of myogenic enzymes (aldolase, 17.6 IU/l and myoglobin, 247.2 ng/ml) and positive titers for the anti-Jo-1 antibody and hypoxia (PaO(2), 79.4 Torr). The chest radiograph revealed a ground-glass opacity. The patient was diagnosed as interstitial pneumonia (IP) associated with polymyositis (PM) at 20 weeks of gestation. On July 9, we commenced the initial treatment-steroid pulse therapy with 60 mg/day of prednisolone and 3 mg/day of tacrolimus. We also induced abortion. The treatment of corticosteroids and tacrolimus was, however, ineffective even after increasing the tacrolimus dose to 6 mg/day. On July 30, she suddenly experienced chest pain along with severe dyspnea. Computed tomography revealed the presence of pneumomediastinum and deterioration of the IP. We added cyclophosphamide pulse therapy to the existing regimen ; this improved the disease course, reduced hypoxia, and improved radiographic findings. We believe that this is a rare case of IP with PM during pregnancy.

Topics: Adult; Cyclophosphamide; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Lung Diseases, Interstitial; Mediastinal Emphysema; Polymyositis; Pregnancy; Pregnancy Complications; Pulse Therapy, Drug; Tacrolimus

Topics: Cardiac Tamponade; Electromyography; Female; Humans; Immunosuppressive Agents; Middle Aged; Polymyositis; Tacrolimus; Treatment Outcome

Topics: Adult; Female; Humans; Immunosuppressive Agents; Middle Aged; Polymyositis; Tacrolimus; Treatment Outcome

Chronic graft versus host disease (GVHD) is a common late complication of hematopoietic stem cell transplantation. Polymyositis is a rare manifestation of chronic GVHD after donor lymphocyte infusion (DLI). Patients with both polymyositis and myocarditis have not been reported to date. Here, we report an 18-year-old female patient who developed polymyositis and myocarditis after a DLI. The patient developed the symptoms of fever, generalized myalgia, dysarthria, and asymptomatic sinus tachycardia at DLI day +102, and 17 days after the discontinuation of immunosuppressants. The laboratory testing showed elevated muscle enzymes, and the electromyographic examination revealed myopathic abnormalities compatible with the diagnosis of myositis. The muscle biopsy showed CD8+ T cell infiltration of the muscle fibers. The electrocardiogram (ECG) showed sinus tachycardia with an incomplete right bundle branch block, anteroseptal ST elevation and lateral ST depression. Echocardiography showed mild hypokinesia of the left interventricular septal wall without evidence of infection or leukemic relapse. The patient was immediately treated with 60 mg/day of prednisone and tacrolimus after the diagnosis of polymyositis and myocarditis, apparently associated with chronic GVHD. The cardiac and muscle enzymes decreased and the ECG normalized after immunosuppressant treatment. The follow-up ECG 2 weeks after initiation of therapy was normal.

Topics: Acute Disease; Adolescent; Anti-Inflammatory Agents; Blood Donors; Chronic Disease; Female; Graft vs Host Disease; Humans; Immunosuppressive Agents; Leukemia; Lymphocyte Transfusion; Myocarditis; Polymyositis; Prednisone; Tacrolimus

Topics: Adrenal Cortex Hormones; Antibodies, Antinuclear; Humans; Immunosuppressive Agents; Lung Diseases, Interstitial; Myography; Polymyositis; Respiration, Artificial; Respiratory Distress Syndrome; Syndrome; Tacrolimus

Polymyositis and interstitial lung diseases, predominantly nonspecific interstitial pneumonia (NSIP), are known to be frequent in antisynthetase syndrome, where anti-aminoacyl-tRNA synthetase antibodies are often identified. An unusual case of acute respiratory distress syndrome, secondary to such proven NSIP of cellular type with predominant CD8 lymphocytes, is described herein. The patient described in the present case study initially had a poor recovery with high dose of steroids, but this was followed by a good improvement after the prescription of tacrolimus and a low dose of prednisone. A precise diagnosis in similar circumstances may be life-saving, allowing the successful application of new immunosuppressants.

Topics: Antibodies, Antinuclear; Autoantibodies; CD8-Positive T-Lymphocytes; Cyclosporine; Humans; Immunosuppressive Agents; Lung Diseases, Interstitial; Male; Middle Aged; Polymyositis; Respiratory Distress Syndrome; Syndrome; Tacrolimus; Tomography, X-Ray Computed; Treatment Outcome

We report a 57 year-old woman with polymyositis and interstitial pneumonia. With the steroid therapy alone, the decline of creatine kinase was insufficient and muscle strength was not improved. After the addition of tacrolimus 3 mg, serum creatine kinase declined, muscle strength was improved, and the dose of steroid could be tapered very smoothly. There was no remarkable change in the status of the interstitial pneumonia on the chest CT, but the vital capacity was improved. The improvement of the respiratory muscle strength might reduce the respiratory symptom and increase the daily activity in this case. It was possible that dose of steroid was tapered early with tacrolimus, and the side effect which accompanies long-term medication of steroids could be avoided. In polymyositis, tacrolimus is very useful medicine in the steroid-resistant case or in the case suffering from the side effect of steroids. There is possibility that tacrolimus becomes one of the choices of the treatment of polymyositis.

Topics: Female; Humans; Immunosuppressive Agents; Middle Aged; Polymyositis; Prednisolone; Tacrolimus

The patient is a 62-year-old man who was diagnosed with myasthenia gravis and invasive thymoma at the age of 45 years, and had received treatment by extended thymectomy and radiotherapy. At the age of 61, he had suffered from a myasthenic crisis, and been administered immunoadsorption therapy under managed ventilatory care. Treatment had then been continued with steroids; however, due to subsequent deterioration of his diabetic state, treatment was switched to the immunosuppressant drug tacrolimus. Three months after the commencement of tacrolimus administration, the patient developed generalized malaise and dyspnea. The serum creatine phosphokinase (CPK) level was abnormally elevated, and abnormal electrocardiographic findings were noted, including atrioventricular dissociation and ventricular escape contraction. Steroid pulse therapy was therefore initiated, however, 4 days later, the patient suddenly died. Autopsy examination revealed inflammatory cell infiltration with giant cells in the myocardium, diffuse myocardial degeneration, and polymyositis. The case was therefore considered as one with the syndrome of myasthenia gravis, polymyositis, giant cell myocarditis, and thymoma.

Topics: Alopecia; Creatine Kinase; Dyspnea; Electrocardiography; Giant Cells; Humans; Immunosuppressive Agents; Male; Middle Aged; Myasthenia Gravis; Myocarditis; Myocardium; Myositis; Polymyositis; Radiography, Thoracic; Tacrolimus; Thymoma; Thymus Neoplasms; Time Factors; Treatment Outcome

We report a patient with polymyositis (PM) associated with myasthenia gravis (MG). Both disorders had been controlled for around 15 years by oral prednisolone and a cholinesterase inhibitor following surgical removal of invasive thymoma and radiotherapy, but muscular weakness due to myalgia and an increase in serum levels of myogenic enzymes, mainly ascribable to the recurrence of PM, reappeared immediately after cessation of these drugs, which was done because the patient had multiple bone fractures and severe osteoporosis due to the long-term corticosteroid therapy. Oral tacrolimus was therefore tried, and produced an improvement in muscular symptoms in association with normalization of myogenic enzymes. PM associated with MG as in this patient might be the best indication for tacrolimus, considering its efficacy in MG, but this drug should also be actively considered as a therapeutic option in refractory cases of PM alone, particularly when either corticosteroids or other immunosuppressive agents are not usable.

Topics: Adrenal Cortex Hormones; Adult; Female; Humans; Immunosuppressive Agents; Myasthenia Gravis; Osteoporosis; Polymyositis; Prednisolone; Tacrolimus; Treatment Outcome

Topics: Adult; Aged; Autoantibodies; Creatine Kinase; Female; Hand Strength; Humans; Immunosuppressive Agents; Lung Diseases, Interstitial; Middle Aged; Polymyositis; Tacrolimus; Treatment Outcome