tacrolimus and Muscle-Weakness

Thymectomy is a standard treatment of myasthenia gravis (MG). Immunomodulating agents are frequently given during the post-thymectomy latency period until complete remission is fully consolidated, but serious side effects is a relevant clinical problem for patients on long-term immunomodulating treatment.. To assess the effectiveness of starting tacrolimus in the immediate postoperative period in MG patients undergoing transsternal extended thymectomy, with complete stable remission (CSR) as the primary outcome of the study.. Forty-eight MG patients received tacrolimus, 0.1 mg/kg per day b.i.d. (started 24 h after thymectomy) and prednisone 1.5 mg/kg/day. Histologically, 34 patients had hyperplasia, 20 thymic involution, and 14 thymoma. Of the 48 patients, 40 completed 1 year of tacrolimus therapy, 38 completed 2 years, 27 completed 3 years, 21 completed 4 years, and 9 more than 5 years. Mean dose of tacrolimus was 4.9 mg/day (range 2-8 mg/day) with a mean plasma drug concentration of 7.6 ng/mL (range 7-9 ng/mL). Prednisone could be withdrawn after the first year in 93.7% of patients and at 2 years in 100%.. The mean follow-up was 24.4 months, SD 17.3 (range 6-60 months). Improvement of muscular strength and decrease of anti-AChR antibodies were statistically significant (p < 0.001) shortly after operation. CSR was obtained in 33.4% of patients, pharmacological remission in 62.6%; 4% of patients had minimal symptoms. None of the patients with thymoma achieved CSR. The estimated median follow-up to obtain a CSR was 37.9 months (95% confidence interval [CI] 26.4-49.5 months). The overall crude CSR rate was 33.4%, with 47% for non-thymoma patients. The probability to achieve CSR at 3 years was 67% for the non-thymomatous group.. Long-term immune-directed treatment with tacrolimus to improve the effectiveness of thymectomy in MG is feasible and was associated with a high rate of CSR in patients without thymoma.

Topics: Adolescent; Adult; Aged; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Male; Middle Aged; Muscle Weakness; Myasthenia Gravis; Postoperative Period; Prednisone; Receptors, Cholinergic; Sternum; Surveys and Questionnaires; Tacrolimus; Thymectomy; Time Factors

Seventy-nine patients with cyclosporine- and prednisone-dependent myasthenia gravis (MG) after thymectomy received tacrolimus for a mean of 2.5 +/- 0.8 years. Prednisone was withdrawn in all but two patients. Anti-acetylcholine antibodies and MG score for disease severity decreased significantly and muscular strength increased by 39%. Complete stable remission was achieved in 5% of patients and pharmacologic remission in 87.3%. All patients resumed full activities of daily living.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents; Ataxia; Autoantibodies; Cyclosporine; Dizziness; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Muscle Weakness; Myasthenia Gravis; Prednisone; Prospective Studies; Receptors, Cholinergic; Remission Induction; Renal Insufficiency; Tacrolimus; Thymectomy; Time; Treatment Outcome

A 69-year-old Japanese woman was admitted to our hospital with progressive muscle weakness and dysphagia. She was taking pitavastatin for dyslipidemia. Her serum creatine kinase was 6,300 U/L. Pitavastatin was stopped, but her symptoms deteriorated, and cardiac congestion appeared. A muscle biopsy showed necrotizing myopathy (NM), and anti-signal recognition particle (SRP) antibody was positive.

Topics: Aged; Autoantibodies; Biopsy; Cardiomyopathies; Contrast Media; Echocardiography; Female; Gadolinium; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Magnetic Resonance Imaging; Multimodal Imaging; Muscle Weakness; Muscle, Skeletal; Muscular Diseases; Positron Emission Tomography Computed Tomography; Signal Recognition Particle; Tacrolimus

An infant boy with steroid-resistant nephrotic syndrome (idiopathic membranous glomerulonephropathy) achieved remission with ciclosporin but developed eosinophilia and high IgE levels (max 19 000  iU/mL). Conversion to tacrolimus resulted in chronic diarrhoea (eosinophilic gastroenteritis), muscle weakness, polyserositis and failure-to-thrive. In contrast, a trial without tacrolimus resulted in a ciclosporin-responsive relapse, therapy-resistant focal seizures with generalised spikes, worsening muscle weakness and diarrhoea. The patient was weaned off of ciclosporin and completely normalised. In vitro testing demonstrated decreased viability of the patient's cells when incubated with calcineurin inhibitors (ciclosporin, 70%; tacrolimus, 80% compared to control cells), supporting their role in this adverse drug reaction.

Topics: Cell Survival; Cyclosporine; Deprescriptions; Drug Substitution; Enteritis; Eosinophilia; Failure to Thrive; Gastritis; Gingival Hyperplasia; Glomerulonephritis, Membranous; Humans; Hypertrichosis; Immunosuppressive Agents; In Vitro Techniques; Infant; Kidney Glomerulus; Male; Microscopy, Electron; Muscle Weakness; Seizures; Serositis; Tacrolimus; Vasculitis

The widespread use of immunosuppressive agents has significantly increased the rates of successful solid-organ and stem cell transplants, especially with liver and kidney. Cyclosporine and tacrolimus are most commonly used for this purpose. Although these agents have different mechanisms of action, both have various adverse effects, including nausea, vomiting, headache, hypertension, nephrotoxicity, and rarely epileptic seizures. In our first case, a patient presented with epileptic seizures and hemiparesis after a liver transplant, and posterior reversible encephalopathy syndrome related to cyclosporine toxicity was considered. Once cyclosporine levels in the blood decreased, the patient had both clinical and radiologic improvements. In our second case, a patient presented with delirium after a liver transplant. Again, when cyclosporine levels in the blood decreased, the patient showed improvement in clinical findings. Neurologic complications may develop after liver transplant, and these complications are encountered most frequently within the first postoperative month. Neurologic complications are multifactorial; insufficient graft function, intracranial bleeding, cerebral infarcts, infections, and immunosuppressive drug toxicity (tacrolimus and cyclosporine) may be considered among these factors. As shown in our presented cases, most neurologic complications can be successfully treated by correcting the underlying factor.

Topics: Cyclosporine; Epilepsy; Female; Humans; Immunosuppressive Agents; Liver Diseases; Liver Transplantation; Middle Aged; Muscle Weakness; Paresis; Postoperative Complications; Reflex, Babinski; 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

Topics: Antihypertensive Agents; Cyclophosphamide; Cyclosporine; Drug Substitution; Drug Therapy, Combination; Fatigue; Glomerulosclerosis, Focal Segmental; Gynecomastia; Humans; Hypertension; Male; Mastodynia; Middle Aged; Muscle Weakness; Mycophenolic Acid; Prednisone; Proteinuria; Tacrolimus

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

Macrophagic myofascitis (MMF) is an unusual inflammatory myopathy characterized by muscle infiltration by macrophages and lymphocytes. Here, we describe a case of MMF which is associated with rheumatoid arthritis. A 53-year-old Japanese rheumatoid arthritis (RA) patient presented with focal tenderness of lower extremities. Magnetic resonance imaging showed evidence of myofascitis involving fascias of anterior tibialis muscle. Muscle biopsy showed a unique pathological pattern of MMF. MMF is known to be associated with vaccination containing aluminum. However, our case was not related to aluminum containing vaccinations and etiologies are unknown. The possible link needs to be discussed.

Topics: Arthritis, Rheumatoid; Biopsy; Fascia; Female; Gait Disorders, Neurologic; Humans; Immunosuppressive Agents; Leg; Macrophages; Magnetic Resonance Imaging; Middle Aged; Muscle Weakness; Muscle, Skeletal; Myofascial Pain Syndromes; Myositis; Prednisolone; Tacrolimus; Treatment Outcome

Topics: Cyclosporine; Female; Humans; Middle Aged; Muscle Weakness; Myositis; Nail Diseases; Pyoderma Gangrenosum; Tacrolimus; Toes; Treatment Outcome

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