tacrolimus and Dermatomyositis

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

A 58-year-old man with anti-melanoma differentiation-associated gene 5-positive dermatomyositis (MDA5-DM) developed Epstein-Barr virus (EBV)-associated malignant lymphoma as other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OIIA-LPD) during the combined immunosuppressive therapy of high-dose prednisolone, tacrolimus, and intravenous cyclophosphamide for MDA5-DM. Serum EBV DNA was detected, and EBV-encoded small RNA was positive in the tissue sample of LPD, indicating that EBV reactivation contributed to the pathogenesis of LPD in our case. The patient underwent chemotherapy, including rituximab, promptly after discontinuation of tacrolimus and cyclophosphamide, resulting in complete remission of the malignant lymphoma, and MDA5-DM has not recurred with 3.5 mg/d of prednisolone monotherapy. We reviewed 19 cases of OIIA-LPD in patients with idiopathic inflammatory myopathies and herein report the first case of MDA5-DM complicated with OIIA-LPD. Among the 19 patients, 7 showed regression of LPD only following withdrawal of immunosuppressants, 9 took chemotherapy for LPD, and 5 died. It should be noted that patients with MDA5-DM-associated rapidly progressive interstitial lung disease could develop OIIA-LPD because they receive aggressive immunosuppressive therapy.

Topics: Cyclophosphamide; Dermatomyositis; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Iatrogenic Disease; Immunosuppressive Agents; Lymphoproliferative Disorders; Male; Middle Aged; Prednisolone; Tacrolimus

Interstitial lung disease (ILD) in patients with polymyositis (PM) and dermatomyositis (DM) is often resistant to treatment and life threatening, being recognized as one of the severest complication in these autoimmune disorders. Patients with clinically amyopathic dermatomyositis (CADM) or those with anti-CADM140/MDA5 antibody are especially prone to develop rapidly progressive interstitial pneumonia. We retrospectively analyzed 46 patients with PM/DM admitted to our hospital and identified DM, rapidly progressive disease, honeycomb lung, CADM and extensive ILD as risk factors for recurrence or death. In the presence of two or more risk factors, the sensitivity and specificity for the prediction of death or relapse were 81.3% and 76.7%, respectively. Calcineurin inhibitors have been widely used as induction and maintenance therapy for PM/DM-associated ILD. Recently we reported the benefit of tacrolimus on the disease-free survival and event-free survival of the patients with PM/DM-associated ILD. Among those patients treated with tacrolimus, poor prognostic factors for death, recurrence or severe adverse event were identified as acute progression of the disease, honeycomb lung, forced vital capacity (FVC) less than 80% and having DM. The potential effectiveness of an intensive therapy protocol with triple therapy that comprises high-dose corticosteroids, calcineurin inhibitors and cyclophosphamide has been reported.

Topics: Adrenal Cortex Hormones; Calcineurin Inhibitors; Cyclophosphamide; Cyclosporine; Dermatomyositis; Drug Therapy, Combination; Humans; Immunosuppressive Agents; Lung Diseases, Interstitial; Prognosis; Retrospective Studies; 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

Topics: Cellulitis; Dermatitis; Dermatomyositis; Facial Dermatoses; Humans; Immunosuppressive Agents; Impetigo; Lupus Erythematosus, Discoid; Ointments; Psoriasis; Rosacea; Tacrolimus

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

The efficacy of combination therapy with corticosteroids and CNI, TAC and CsA, for PM/DM-ILD has been described retrospectively. However, it remains unknown which CNI treatment regimens, TAC or CsA regimens, are more effective as initial treatments for patients with PM/DM-ILD.. We conducted a prospective multicentre, open-label, randomized, 52-week phase 2 trial. Patients with PM/DM-ILD were randomly allocated to receive PSL plus TAC (TAC group) or PSL plus CsA (CsA group). The primary endpoint was PFS rate in the intention-to-treat population at 52 weeks. The secondary endpoints were OS rate at 52 weeks, changes in pulmonary function tests from baseline to 52 weeks and AE.. Fifty-eight patients were randomly assigned to the TAC group (n = 30) and the CsA group (n = 28). The PFS rates at 52 weeks were 87% in the TAC group and 71% in the CsA group (P = 0.16). The OS rates at 52 weeks were 97% in the TAC group and 93% in the CsA group (P = 0.50). The %FVC at 52 weeks in the per-protocol populations significantly increased in both groups. None of the patients discontinued the treatment due to AE.. PSL plus TAC treatment may achieve a better short-term PFS rate compared with PSL plus CsA treatment. Further studies must be conducted to evaluate the long-term efficacy and safety of such treatment.

Topics: Cyclosporine; Dermatomyositis; Humans; Immunosuppressive Agents; Lung Diseases, Interstitial; Prednisolone; Prospective Studies; Retrospective Studies; 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

Dermatomyositis is an inflammatory disease primarily involving the striated muscles and skin. Muscle disease usually responds to aggressive therapy with systemic corticosteroids. However, cutaneous lesions can be very resistant to systemic and topical therapies, even in combination. More treatment options are needed. Tacrolimus is an immunomodulator now available in a topical ointment.. To study the treatment of patients with refractory cutaneous lesions of dermatomyositis using topical tacrolimus 0.1% ointment.. Six patients with recalcitrant cutaneous lesions of dermatomyositis were included in this brief observational study: five adults and one pediatric patient. Five patients had classic dermatomyositis and one had dermatomyositis sine myositis.. All had some degree of improvement of their dermatologic disease following 6-8 weeks of treatment with topical tacrolimus 0.1% ointment. Two had dramatic responses (>90% improvement), one had moderate (40-90%) improvement and three had minimal (20-40%) improvement.. The dermatologic manifestations of dermatomyositis can be very difficult to treat. Multiple systemic and topical therapies have been studied. Combinations of treatments are often used, sometimes still not successfully. The results of this brief observational study using topical tacrolimus ointment for the treatment of refractory cutaneous lesions of dermatomyositis are encouraging. Topical tacrolimus was a useful adjunct in the treatment of the dermatologic component of dermatomyositis in adults and children in this pilot study.

Topics: Administration, Cutaneous; Aged; Child, Preschool; Dermatomyositis; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Ointments; Pilot Projects; Tacrolimus

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

The high-dose glucocorticosteroid (GC) treatment is the first choice for dermatomyositis complicated with interstitial lung disease (DM-ILD) but patients are resistant to the high-dose GC monotherapy. Besides, the high dose of GC, the secondary immunosuppressive agent(s) is necessary but there is controversy for the selection of immunosuppressive agent(s). The objectives of the study were to analyze the efficacy of different therapeutic options for DM-ILD to identify the optimal therapy. A total of 60 patients had received intravenous 1.0-2.0 mg/ kg/day prednisolone for DM-ILD. In severe conditions, patients had received oral 1 to 3 mg/day tacrolimus (TAC), 500 mg/ m2/month cyclophosphamide (CY), and/or 1 g/ day methylprednisolone pulse (TI cohort, n = 24). In severe conditions, patients had received 1 g/day methylprednisolone pulse and 2-3 mg/ kg/day cyclosporine A (CsA) and/or 500 mg/ m2/month CY (existing historical treatment; CT cohort, n = 36). Patients of the TI cohort did not receive CsA. Patients in the CT cohort were received CY in significantly fewer numbers than those of the TI cohort during treatment (P = .0112). A total of 11 (46%) patients from the TI cohort and 14 (39%) patients from the CT cohort were developed relapsed. At the end of the 30-months, higher numbers of patients of the TI cohort had an event(s) free survival than those of the CT cohort (7 (29%) vs 2 (6%), P = .0229). Also, higher numbers of patients of the TI cohort had survived irrespective of an event(s) than those of the CT cohort (21 (87%) vs 22 (61%), P = .0399). Patients of the TI cohort had developed herpes zoster (2 (8%)) and cytomegalovirus (4 (17%)) infections. Patients of the CT cohort developed renal dysfunction (10 (28%)). Hyperglycemia, hyperlipidemia, and fracture (GC-related toxicities) were also reported in both cohorts and these toxicities were fever in the TI cohort. The addition of TAC to high doses GC with CY is an ideal treatment for severe conditions of DM-ILD (Level of Evidence: III; Technical Efficacy Stage: 4).

Topics: Cyclophosphamide; Cyclosporine; Dermatomyositis; Drug Therapy, Combination; Humans; Immunosuppressive Agents; Lung Diseases, Interstitial; Methylprednisolone; Retrospective Studies; Tacrolimus

The efficacy of tofacitinib (TOF) in the early diagnosis of melanoma differentiation-associated gene 5 (MDA5)-related interstitial lung disease (ILD) has been described. However, whether TOF exposure is associated with a reduced 1-year mortality rate remains undetermined.. Patients diagnosed with MDA5-ILD receiving TOF or tacrolimus (TAC) treatment were included. A Cox proportional hazards model, which was adjusted for age, sex, smoking history, anti-MDA5 antibody titers, and concurrent use of other steroid-sparing agents, was performed to compare all-cause mortality and to investigate the risk factors predicting 1-year mortality rates in the 2 treatment groups.. During the study period, 26 patients were treated with TOF and 35 were treated with TAC. The 6-month (38.5% vs 62.9%;. Our observational study showed that TOF use might have a potential effect on improving the outcomes of MDA5-ILD. Future clinical trials are needed to assess the long-term efficacy and tolerability of TOF.

Topics: Autoantibodies; Dermatomyositis; Humans; Interferon-Induced Helicase, IFIH1; Lung Diseases, Interstitial; Melanoma; Retrospective Studies; Tacrolimus

Immunosuppressive therapy is the main treatment for patients with interstitial lung diseases (ILD) secondary to dermatomyositis (DM). Microbial colonization or infection might be very common for these patients. However, the relationship between immunotherapy and microorganism isolates are not fully understood in these patients.. This study retrospectively analyzed on the clinical features in DM-ILD patients who had positive microbiological results during immunosuppressive therapy in our hospital.. Patients were divided into two groups, according to the result of microbiological study. Comparisons in infection-related data in various contexts were carried out.. Occurrence of positive isolates in DM-ILD patients may relate to higher inflammatory markers CRP, lower CD4 + T cells counts, high concentration of serum FK-506, and longer hospital stay.

Topics: Autoantibodies; Dermatomyositis; Humans; Immunosuppression Therapy; Lung Diseases, Interstitial; Prognosis; Retrospective Studies; Tacrolimus

Interstitial lung disease (ILD) accompanied by anti-melanoma differentiation-associated gene 5 (anti-MDA-5)-positive dermatomyositis (DM) is often rapidly progressive and associated with poor prognosis. Because there is no established treatment, we undertook this study to prospectively evaluate the efficacy and safety of a combined immunosuppressive regimen for anti-MDA-5-positive DM patients with ILD.. Adult Japanese patients with new-onset anti-MDA-5-positive DM with ILD (n = 29) were enrolled at multiple study centers from 2014 to 2017. They were treated with a regimen of high-dose glucocorticoids (GCs), tacrolimus, and intravenous cyclophosphamide (IV CYC). Plasmapheresis was used if a patient's condition worsened after the regimen started. The primary end point was 6-month survival, which was compared between this group of patients and a historical control group (n = 15) consisting of anti-MDA-5-positive DM patients with ILD who received step-up treatment (high-dose GC and stepwise addition of immunosuppressant). Secondary end points were 12-month survival rate, adverse events, and changes in laboratory data.. The combined immunosuppressive regimen group showed significantly higher 6-month survival rates than the step-up treatment group (89% versus 33%; P < 0.0001). Over a period of 52 weeks, improvements in anti-MDA-5 titers, serum ferritin levels, vital capacity, and chest high-resolution computed tomography scores were observed. The combined immunosuppressive regimen group received IV CYC nearly 20 days earlier with shorter intervals and tended to receive plasmapheresis more often than patients undergoing step-up treatment. Cytomegalovirus reactivation was frequently observed over 52 weeks.. A combined immunosuppressive regimen is effective for anti-MDA-5-positive DM patients with ILD. Plasmapheresis can be used for additional effect in intractable disease. Patients should be carefully monitored for opportunistic infections during treatment.

Topics: Adult; Autoantibodies; Cyclophosphamide; Dermatomyositis; Disease Progression; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Interferon-Induced Helicase, IFIH1; Japan; Lung Diseases, Interstitial; Male; Prospective Studies; Survival Rate; Tacrolimus; Treatment Outcome

Rapidly progressive interstitial lung disease (RP-ILD) with poor prognosis often accompanies anti-melanoma differentiation-associated gene 5 (MDA5)-positive DM. Combined immunosuppressive therapy, including glucocorticoids, calcineurin inhibitors and intravenous cyclophosphamide (IVCY) is reportedly effective in DM with RP-ILD, but some patients remain resistant to therapy. We examined the utility of plasma exchange (PE) in such intractable cases and investigated the prognostic factors of the disease.. Thirty-eight anti-MDA5-positive DM-ILD patients who received the combined immunosuppressive therapy were retrospectively reviewed. Their serum cytokines were evaluated by multiplex assay before treatment. The patients were divided into two groups: those who achieved remission without exacerbation of respiratory dysfunction (n = 25, group A) and those who progressed to hypoxemia during the treatment (n = 13, group B).. PE was carried out in eight group B patients, but none of group A. Five of the eight treated with PE survived, while the five untreated patients died (P =0.04). Higher neutrophil lymphocyte ratio, higher serum ferritin, hypoxemia, high-resolution computed tomography (HRCT) score before treatment and increase of Krebs von Lungen-6 (KL-6) in the first 4 weeks of the treatment were the prognostic factors for disease progression. Serum cytokines such as IL-1, IL-6, IL-8, IL-10, IL-12p70, IL-18 and sCD163 levels were higher in group B than group A.. PE should be an effective adjuvant treatment in anti-MDA5-positive DM with RP-ILD. Assessment of basal laboratory tests or monocyte/macrophage-derived cytokines and the increase of KL-6, HRCT score and hypoxemia may help us to predict intractable cases and to make early treatment decisions regarding PE in anti-MDA5-positive DM.

Topics: Adult; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Autoantibodies; Cyclosporine; Dermatomyositis; Drug Resistance; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Interferon-Induced Helicase, IFIH1; Interferons; Interleukins; Japan; Lung Diseases, Interstitial; Male; Middle Aged; Plasma Exchange; Receptors, Cell Surface; Tacrolimus

A 74-year-old man was administered nivolumab to treat recurrent squamous cell carcinoma of the lungs. He developed fatigue, redness on the front of his neck, muscle weakness, and difficulty in swallowing after receiving the third course of nivolumab. Physical and neurological examinations showed proximal limb muscle weakness, periorbital erythema, and erythema of the front of his neck as well as fingers. Laboratory investigations revealed elevated serum CK and aldolase levels, and he was diagnosed with dermatomyositis. We initiated steroid pulse therapy and intravenous immunoglobulin therapy; however, he died of advanced lung cancer. Immune checkpoint inhibitor-induced neuromuscular disease is increasingly being observed in clinical practice. We report a rare case of dermatomyositis with squamous cell carcinoma of the lungs secondary to nivolumab treatment.

Topics: Aged; Antineoplastic Agents, Immunological; Autoantibodies; Carcinoma, Squamous Cell; Dermatomyositis; Fatal Outcome; Humans; Immune Checkpoint Inhibitors; Immunoglobulins, Intravenous; Immunotherapy; Lung Neoplasms; Male; Methylprednisolone; Nivolumab; Pulse Therapy, Drug; Tacrolimus; Transcription Factors

We assessed the efficacy and safety of combination therapy with glucocorticoids and high-trough level tacrolimus (TAC) for the treatment of acute/subacute interstitial pneumonia (A/SIP) in patients with dermatomyositis (DM).. Eleven DM-A/SIP patients were enrolled. The combination therapy with glucocorticoids and TAC was started as early as possible after DM-A/SIP was diagnosed. We monitored the trough concentration of TAC. In the initial 3 months, we maintained the trough concentration of TAC at relatively high levels within a range of 15-20 ng/mL. Then, we decreased the TAC doses stepwise to keep the trough concentration at 10-15 ng/mL in the next 3 months and 5-10 ng/mL as a maintenance dose.. Seven patients had clinically amyopathic DM. Six patients were positive for anti-aminoacyl-tRNA synthetase antibody and two were positive for anti-melanoma differentiation-associated gene 5 antibody. Ten patients survived for the period of the 24-week follow up. One patient died under a tentative diagnosis of viral encephalitis at 4 months after the treatment. In the 10 surviving patients, interstitial pneumonia improved in eight patients and was not worse in two patients. Clinical examinations, including the Krebs von den Lungen-6 levels, % forced vital capacity, and chest computed tomography score, were significantly improved by this combination therapy. Although grade 1 and 2 renal damage occurred in 4 and 2 patients, respectively.. The present findings suggest that early therapeutic intervention by a combination with glucocorticoids and initial high-trough level TAC is effective for DM-A/SIP although consideration of the risks of infection and renal damage is required.

Topics: Acute Disease; Adult; Aged; Dermatomyositis; Drug Monitoring; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Lung Diseases, Interstitial; Male; Middle Aged; Retrospective Studies; Risk Factors; Tacrolimus; Time Factors; Treatment Outcome

Clinically amyopathic dermatomyositis with anti-Melanoma Differentiation-Associated gene 5 (MDA5) antibody often presents with severe interstitial lung disease. Although serum ferritin level is known to reflect interstitial lung disease activity, there are few case reports describing this association.. A 58-year-old man was referred to our outpatient clinic with a 3-week history of cough and respiratory distress. He had erythema over the V area of the neck and a Gottron's sign. Chest computed tomography revealed diffuse ground-glass opacities and reticular shadows in both lungs. Test for anti-MDA5 antibody was positive. After admission, he received triple combination therapy (methylprednisolone pulse therapy, tacrolimus, and cyclophosphamide). However, his respiratory condition worsened as the serum ferritin level increased. Despite no apparent deterioration on chest radiography, he ultimately died due to respiratory failure.. In this case, triple combination therapy was not effective for the patient's respiratory condition. The serum ferritin level was correlated with disease activity and was more useful than chest radiography for monitoring clinical status.

Topics: Anti-Inflammatory Agents; Cyclophosphamide; Dermatomyositis; Disease Progression; Drug Therapy, Combination; Fatal Outcome; Ferritins; Humans; Immunosuppressive Agents; Lung Diseases, Interstitial; Male; Methylprednisolone; Middle Aged; Severity of Illness Index; Tacrolimus

A 56-year-old Japanese woman with muscle weakness, increased creatine kinase and aldolase levels, and characteristic cutaneous lesions was diagnosed with anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5 antibody)-positive dermatomyositis. She also had interstitial lung disease (ILD). After corticosteroid and tacrolimus combination therapy was started, bicytopenia and elevated serum ferritin and transaminase emerged. Because the bone marrow tissues were hypoplastic with hemophagocytes, she was diagnosed with concomitant autoimmune-associated hemophagocytic syndrome (HPS). Intravenous cyclophosphamide pulse therapy and plasmapheresis were performed. The laboratory findings indicated improved abnormalities, and the ILD did not progress. Anti-MDA5 antibody-positive dermatomyositis can be complicated by HPS.

Topics: Adrenal Cortex Hormones; Autoantibodies; Combined Modality Therapy; Cyclophosphamide; Dermatomyositis; Disease Progression; Female; Humans; Immunosuppressive Agents; Interferon-Induced Helicase, IFIH1; Lung Diseases, Interstitial; Lymphohistiocytosis, Hemophagocytic; Methylprednisolone; Middle Aged; Plasmapheresis; Pulse Therapy, Drug; Tacrolimus

Topics: Anti-Inflammatory Agents; Autoantibodies; Dermatomyositis; Drug Eruptions; Early Detection of Cancer; Electromyography; Erythema; Humans; Immunosuppressive Agents; Male; Methotrexate; Methylprednisolone; Middle Aged; Skin; Tacrolimus; Transcription Factors; Treatment Outcome

Autoantibodies to melanoma differentiation-associated protein 5 (MDA5) are associated with a subset of patients with dermatomyositis (DM) who have rapidly progressive interstitial lung disease (RP-ILD) with poor prognosis. Intensive immunosuppressive therapy is initiated before irreversible lung damage can occur; however, there are few lines of evidence for the treatment of RP-ILD. Here, we report three cases of anti-MDA5 antibody-associated DM with RP-ILD in which the patients were treated with combined-modality therapy, including high-dose prednisolone, tacrolimus, intravenous cyclophosphamide and intravenous immunoglobulin (IVIG). In all three cases, serum ferritin levels, which are known to represent the disease activity of RP-ILD, were decreased after IVIG administration. IVIG might contribute to the control of the disease activity of anti-MDA5 antibody-positive DM. Moreover, palmar violaceous macules/papules around the interphalangeal joints, which was observed in all three cases in the incipient stage, might be a useful sign in suggesting a diagnosis of anti-MDA5 antibody-associated DM.

Topics: Aged; Anti-Inflammatory Agents; Autoantibodies; Combined Modality Therapy; Cyclophosphamide; Dermatomyositis; Female; Hand Dermatoses; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Interferon-Induced Helicase, IFIH1; Lung Diseases, Interstitial; Male; Middle Aged; Prednisolone; Tacrolimus; Treatment Outcome

Topics: Autoantibodies; Dermatomyositis; Drug Monitoring; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Interferon-Induced Helicase, IFIH1; Lung Diseases, Interstitial; Male; Middle Aged; Prognosis; Ribonucleosides; Severity of Illness Index; Tacrolimus; Tomography, X-Ray Computed; Treatment Outcome

Topics: Cardiomyopathy, Hypertrophic; Dermatomyositis; Female; Humans; Immunosuppressive Agents; Middle Aged; Tacrolimus

Topics: Administration, Topical; Adrenal Cortex Hormones; Adult; Aged; Aged, 80 and over; Dermatomyositis; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Prognosis; Retrospective Studies; Tacrolimus; Treatment Outcome

Topics: Adrenal Cortex Hormones; Cyclophosphamide; Dermatomyositis; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Lung Diseases, Interstitial; Middle Aged; Rituximab; Tacrolimus; Treatment Outcome

We evaluated the safety and effectiveness of adjunctive tacrolimus therapy with conventional immunosuppression in patients with severe connective tissue disease-related interstitial lung disease (CTD-ILD). We included patients from our interstitial lung disease (ILD) registry with CTD-ILD, in whom tacrolimus was added to corticosteroids and an additional immunosuppressive agent. Demographic data, clinical features, lung function, radiographic images, and pathologic findings were reviewed. Effectiveness was assessed by comparing pulmonary function tests (PFTs) closest to tacrolimus initiation to PFTs approximately 6-12 months later. Corticosteroid dose at these time points was also evaluated. We report adverse events attributed to tacrolimus. Seventeen patients with CTD-ILD were included in adverse event analysis; twelve were included in efficacy analysis. Length of tacrolimus therapy ranged from 6 to 110 months (mean 38.8 months ± 31.4). The mean improvement in percent predicted total lung capacity was 7.5% ± 11.7 (p = 0.02). Forced vital capacity mean improvement was 7.4% ± 12.5 (p = 0.06). The average decrease in corticosteroid dose at follow-up was 20.3 mg ± 25.2 (p = 0.02) with complete discontinuation in six patients. No patients experienced a life-threatening adverse event attributed to tacrolimus. Tacrolimus can be effective and is well tolerated as an adjunctive therapy and allows tapering of corticosteroids.

Topics: Adrenal Cortex Hormones; Adult; Aged; Anti-Inflammatory Agents; Connective Tissue Diseases; Dermatomyositis; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Lung Diseases, Interstitial; Male; Middle Aged; Monitoring, Physiologic; Radiography; Respiratory Function Tests; Retrospective Studies; Tacrolimus; Total Lung Capacity; Treatment Outcome; Vital Capacity

The purpose of this study was to investigate the therapeutic advantage of administering tacrolimus (TAC) in patients with polymyositis (PM) and dermatomyositis (DM).. We retrospectively analyzed the clinical outcomes after initiating treatment in 66 patients with PM/DM (28 PM and 38 DM). After initiating treatment, the prognosis was compared between patients who received TAC in combination with prednisolone (PSL) (the concomitant TAC group), and patients who were treated with PSL alone. The therapeutic efficacy of TAC was also evaluated for patients in the concomitant TAC group as well as patients who started additional TAC treatment after relapse (the additional TAC group), by analyzing clinical results, including serum creatine kinase (CK) levels, muscle strength and the daily dose of PSL.. Patients in the concomitant TAC group had significantly lower frequency of relapse and longer periods of remission than patients who were treated with PSL alone (P = 0.0001, P = 0.001, respectively). Significant decreases in CK levels were observed 1 month after starting TAC treatment in both the concomitant TAC group and the additional TAC group. Moreover, the significant effects of withdrawing PSL were also demonstrated in both groups.. Concomitant use of TAC with PSL clearly provides a favorable outcome in patients with DM/PM. Furthermore, additional treatment with TAC is useful for improving prognosis even after recurrence.

Topics: Adult; Aged; Dermatomyositis; Disease-Free Survival; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Kaplan-Meier Estimate; Male; Middle Aged; Prednisolone; Recurrence; Remission Induction; Retrospective Studies; Tacrolimus; Time Factors; Treatment Outcome

Topics: Antibodies; Dermatomyositis; Fingers; Humans; Immunosuppressive Agents; Interferon-Induced Helicase, IFIH1; Lung Diseases, Interstitial; Male; Middle Aged; Prednisone; Respiratory Function Tests; Skin Diseases, Papulosquamous; Skin Ulcer; Tacrolimus; Tomography, X-Ray Computed

Macrophage activation syndrome (MAS), also known as secondary hemophagocytic lymphohistiocytosis, is mediated by cytokine overproduction from excessive activation of T lymphocytes and macrophages. We present a dermatomyositis patient with MAS, caused by hypercytokinemia. The combination of tacrolimus and plasma exchange therapy was effective in this case for treating MAS. This combination therapy is especially useful for MAS refractory to steroids.

Topics: Combined Modality Therapy; Dermatomyositis; Humans; Immunosuppressive Agents; Macrophage Activation Syndrome; Male; Middle Aged; Plasmapheresis; 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

To date, no study has compared the clinical characteristics, malignancy associations, and treatment of dermatomyositis in predominantly Caucasian vs. Asian populations.. This prospective study was conducted to compare clinical characteristics of dermatomyositis, its relationship to malignancy, and treatment between two tertiary medical centers in the USA and Singapore. A total of 19 newly-diagnosed patients in the USA and 15 patients in Singapore were enrolled. Dermatomyositis or amyopathic dermatomyositis were diagnosed based on clinical assessment, skin and muscle biopsies, and muscle testing.. Ninety-five percent of patients in the USA group were of Caucasian descent, while 93% of patients in the Singapore group were of Chinese descent. Both groups were predominantly female. Pruritus was the most common initial symptom reported in both groups, while periungual erythema and Gottron's papules were the most common skin presentations. Heliotrope eruption was more common in the Singapore group, occurring in 80% of patients vs. 32% of patients in the USA group (P = 0.007). Three patients in the Singapore group developed a malignancy, with two of these patients having nasopharyngeal carcinoma. None of the USA patients developed malignancies in a follow- up period of 2-5 years. Immunosuppressive steroid sparing therapy with hydroxychloroquine was more frequently used in Singapore, while topical tacrolimus was more frequently used in the USA.. The clinical presentations of dermatomyositis vary among different ethnic populations. Chinese patients with dermatomyositis have a significant risk for nasopharyngeal carcinoma.

Topics: Adrenal Cortex Hormones; Adult; Aged; Antibodies, Monoclonal, Murine-Derived; Asian People; Bone Density Conservation Agents; Calcium Compounds; Carcinoma; Dermatomyositis; Dietary Supplements; Diphosphonates; Erythema; Female; Humans; Hydroxychloroquine; Immunosuppressive Agents; Male; Methotrexate; Middle Aged; Mycophenolic Acid; Nasopharyngeal Neoplasms; Oxides; Prospective Studies; Pruritus; Rituximab; Singapore; Tacrolimus; Tertiary Care Centers; United States; Vitamin D; White People

To investigate whether or not coadministration of tacrolimus (TAC) with prednisolone (PSL) can produce a beneficial effect in the treatment of polymyositis/ dermatomyositis (PM/DM).. We reviewed medical records of 32 PM/DM patients who had been admitted to our hospital, and abstracted those who had received TAC in addition to oral PSL for treatment. The clinical usefulness of TAC in PM/DM was objectively evaluated focusing upon the manual muscle strength test (MMT) score, serum creatine kinase (CK) and tapering of PSL.. Nine patients with PM and 6 with DM were enrolled in this study. TAC was added because of difficulty in reduction of PSL in 12 patients and recurrence with corticosteroid-induced complications in the remaining 3. Both PM and DM patients showed significant increases in the MMT score and significant decreases in serum CK 1 to 3 months after starting TAC compared with before. Skin symptoms in a clinically amyopathic DM patient also improved 1 month after starting TAC. The daily dosage of PSL could be significantly reduced in both PM and DM after starting TAC compared with before. No serious adverse events ascribable to TAC occurred in any patients.. Additional use of TAC with PSL may safely promote improvement of PM/DM and also accelerate tapering of the latter.

Topics: Administration, Oral; Adrenal Cortex Hormones; Adult; Aged; Aged, 80 and over; Biomarkers; Creatine Kinase; Dermatomyositis; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Muscle Strength; Muscle, Skeletal; Prednisolone; Recovery of Function; Retrospective Studies; Tacrolimus; Time Factors; Treatment Outcome; Young Adult

Case study A man, 77 years of age, presented with haematemesis, abdominal pain and increasing limb weakness. He also had a skin rash on his chest and face.

Topics: Administration, Topical; Aged; Dermatomyositis; Diagnosis, Differential; Exanthema; Glucocorticoids; Humans; Immunosuppressive Agents; Male; Muscle Weakness; Tacrolimus

A 76-year-old woman presented with a pruritic photodistributed rash and dysphagia. Serum anti-nuclear antibody was positive (titre 1/1280) and skin and muscle biopsies confirmed a diagnosis of dermatomyositis. She was treated with oral prednisolone (5-50 mg/day), mometasone furoate 0.1% ointment and lotion, and tacrolimus 0.03% ointment. Four years later she presented with multiple painful scaly erosions on the face, scalp and trunk. Histopathology and direct and indirect immunofluorescence confirmed a diagnosis of pemphigus vulgaris. Repeated malignancy screens were negative. She was treated with methotrexate (10 mg/week) and prednisolone (50 mg/day slowly tapered to 5 mg/day), with good control of both diseases.

Topics: Aged; Anti-Inflammatory Agents; Antibodies, Antinuclear; Dermatomyositis; Female; Humans; Methotrexate; Mometasone Furoate; Pemphigus; Prednisolone; Pregnadienediols; Tacrolimus

A 56-year-old HTLV-I-positive woman, initially diagnosed as having Sjögren's syndrome, presented with muscle weakness, myalgia, face erythema and leg edema. Based on the presence of various autoantibodies, the diagnosis of overlap syndrome (dermatomyositis/Sjögren's syndrome) was made. Treatment with high-dose corticosteroid plus cyclosporine improved her symptoms. However, three months after the start of these treatments, exacerbation of myositis occurred. A muscle biopsy revealed prominent perivascular accumulation of mononuclear cells with perifascicular atrophy, which were consistent with dermatomyositis. Tacrolimus, which was substituted for cyclosporine led to marked improvement of the myositis symptoms.

Topics: Dermatomyositis; Female; HTLV-I Infections; Human T-lymphotropic virus 1; Humans; Middle Aged; Sjogren's Syndrome; Tacrolimus; Treatment Outcome

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 58-year-old male was admitted to our hospital because of periungual nailfold an erythema and erythematous rash on the dorsal joints of his hands and feet, but no muscle weakness. He was thus diagnosed to have amyopathic dermatomyositis. He had moderate hypoxemia and his chest computed tomography scans demonstrated bilateral ground-glass opacities, implicating complication with interstitial pneumonia. Therapy was initiated with pulsed methylprednisolone followed by high-dose corticosteroids, pulsed cyclophosphamide, and cyclosporine. The skin manifestations improved; however, the pulmonary infiltrates and hypoxemia deteriorated during the 2-month period of the treatment. The treatment was switched from cyclosporine to tacrolimus because of an inadequate clinical response to the therapy, and this resulted in the resolution of interstitial pneumonia. This case indicates that tacrolimus administration should be considered for patients with this life-threatening disorder when it is judged to be refractory to cyclosporine.

Topics: Adrenal Cortex Hormones; Cyclophosphamide; Cyclosporine; Dermatomyositis; Drug Therapy, Combination; Humans; Immunosuppressive Agents; Lung Diseases, Interstitial; Male; Middle Aged; Tacrolimus; Treatment Failure

A 67-year-old woman was admitted to our hospital because of erythema in the eyelids and fingers of both hands. Slight muscle weakness in the proximal limbs, a heliotrope rash, Gottron's sign, and mechanic's hand were observed. Creatine kinase serum levels were slightly elevated (376U/l), and the patient tested negative for all autoantibodies except for the antinuclear antibody. Chest computed tomography showed interstitial pneumonia (IP). Based on these findings, the patient was given a diagnosis of dermatomyositis (DM) associated with IP. Combined prednisolone (1 mg/kg/day) and cyclosporin-A (Cy-A 4 mg/kg/day) therapy was initiated; the patient showed marked improvement, but the Cy-A caused liver damage. Therefore, Cy-A was tapered off, and tacrolimus was simultaneously started, initially at a dose of 1 mg/day, building up to a sustained dose of 4 mg/day. The patient's IP and liver condition improved. Tacrolimus is a useful drug for the treatment of DM-IP in cases where Cy-A causes intolerable adverse reactions.

Topics: Cyclosporine; Dermatomyositis; Female; Humans; Immunosuppressive Agents; Lung Diseases, Interstitial; Middle Aged; Tacrolimus

Pulmonary fibrosis associated with amyopathic dermatomyositis is known to have a generally aggressive course and is ultimately fatal. We report the case of a 50-year-old patient with amyopathic dermatomyositis, who developed progressive interstitial pneumonia that was unresponsive to corticosteroids and multiple immunosuppressive agents, including cyclosporine and tacrolimus hydrate. Five courses of lecithinized superoxide dismutase were administered without adverse effects. Improvements in physiological parameters, such as pulmonary function and exercise tolerance, as well as the serum Krebs von den Lungen 6 level, were observed. This is the first report of a case of steroid-refractory interstitial pneumonia treated with lecithinized superoxide dismutase.

Topics: Adrenal Cortex Hormones; Cyclosporine; Dermatomyositis; Exercise Tolerance; Humans; Immunosuppressive Agents; Lung Diseases, Interstitial; Male; Methylprednisolone; Middle Aged; Mucin-1; Phosphatidylcholines; Prednisolone; Pulmonary Fibrosis; Radiography; Respiratory Function Tests; Superoxide Dismutase; Tacrolimus; Treatment Outcome

Topics: Administration, Topical; Blepharitis; Chloroquine; Dermatomyositis; Female; Humans; Immunosuppressive Agents; Injections, Intravenous; Middle Aged; Paraneoplastic Syndromes; Tacrolimus; Treatment Outcome

We report the clinical course of three patients with refractory juvenile dermatomyositis (JDM) who were treated with tacrolimus. All three children had extensive skin disease and severe muscle weakness and were corticosteroid dependent. All three patients showed impressive improvement of mainly the cutaneous lesions. Furthermore, overall disease activity decreased, all children became more physically active, and corticosteroid treatment could be tapered. However, none of the patients showed recovery of muscle strength, which was most likely due to irreversible muscle damage related to the long-standing myositis and/or high-dose steroid treatment. Patients were followed up for 7 to 9 months after the introduction of tacrolimus. No adverse effects were seen. These cases demonstrate that tacrolimus has beneficial effects in children with refractory JDM, especially in those with severe cutaneous manifestations.

Topics: Calcineurin Inhibitors; Child; Child, Preschool; Dermatomyositis; Female; Humans; Male; Remission Induction; Tacrolimus

Dermatomyositis is an inflammatory myopathy associated with an increased risk of mortality due to visceral involvement. Cutaneous involvement has no vital impact but considerably affects the quality of life of the patients and can resist to classical therapies. More treatment options are needed. We report here the case of three patients presenting resistant cutaneous lesions of dermatomyositis successfully treated with topical tacrolimus.. A dramatic cure of the lesions of the face and the hands and a moderate response of other areas were observed without adverse effects.. Tacrolimus is an immunosuppressive agent and topical tacrolimus is used for the treatment of atopic dermatitis and has been occasionally used to treat skin involvement of some systemic inflammatory diseases. Topical tacrolimus seems to be a good therapeutic alternative for resistant skin lesions of dermatomyositis. It could also be proposed as a first intention therapy because of its good tolerance.

Topics: Administration, Cutaneous; Aged; Dermatomyositis; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Tacrolimus; Treatment Outcome

To analize the response to treatment with oral tacrolimus in severe juvenile dermatomyositis.. Clinical charts of the patients diagnosed at our hospital as having definite juvenile dermatomyositis between 1998 and 2004, who have completed 12 months of treatment with oral tacrolimus, were reviewed retrospectively. The MMT (Manual Muscle Testing)-Kendall scale, the MDAA (Myosits Disease Activity Assessment), and the Riley et al score were used for the evaluation of the muscular and skin response.. The study included 6 patients, (evolution: 0.16-11 years). At the end of the follow-up period (12 months) there was a significant improvement at both, muscular and cutaneous level in all patients. Side effects were not observed. Tapering of the daily corticosteroids dose was also possible.. Oral tacrolimus therapy seems to be an effective and safe alternative in cases of severe juvenile dermatomyositis, especially in those with an important cutaneous involvement.

Topics: Age of Onset; Child; Child, Preschool; Dermatomyositis; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Male; Retrospective Studies; Tacrolimus; Treatment Outcome

Topics: Administration, Cutaneous; Dermatomyositis; Female; Humans; Immunosuppressive Agents; Middle Aged; Tacrolimus

Topics: Adult; Dermatologic Agents; Dermatomyositis; Drug Resistance; Drug Therapy, Combination; Follow-Up Studies; Glucocorticoids; Humans; Immunosuppressive Agents; Male; Tacrolimus; Treatment Outcome

Topics: Adolescent; Biological Availability; Cyclosporine; Dermatomyositis; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Prednisolone; Tacrolimus

Topics: Administration, Topical; Adult; Child; Dermatomyositis; Humans; Immunosuppressive Agents; Middle Aged; Skin; Tacrolimus; Treatment Failure

Topics: Adult; Dermatomyositis; Female; Humans; Immunosuppressive Agents; Muscle Weakness; Tacrolimus; Treatment Outcome

Topics: Administration, Oral; Child; Child, Preschool; Dermatomyositis; Heart Transplantation; Heart-Lung Transplantation; Humans; Immunosuppressive Agents; Infant; Intestines; Liver Transplantation; Tacrolimus; Transplantation, Homologous; Viscera