tacrolimus and Arthralgia

Calcineurin inhibitor-induced pain syndrome is an entity recognized in patients on immunosuppressive therapy after transplantation. Diagnosis is characterized by onset of pain beginning in the setting of an elevated calcineurin-inhibitor trough level. Reducing the medication dose relieves symptoms. Imaging findings can be nonspecific, including bone marrow edema and periosteal reaction. We present the unique case of calcineurin inhibitor-induced pain syndrome in a child and review the imaging findings.

Topics: Arthralgia; beta-Thalassemia; Bone Marrow Transplantation; Calcineurin Inhibitors; Female; Humans; Immunosuppressive Agents; Infant; Magnetic Resonance Imaging; Syndrome; Tacrolimus

To determine whether myalgias/arthralgias occurring in cancer patients who receive quinupristin/dalfopristin are associated with biliary tract dysfunction.. We studied 56 patients with vancomycin-resistant enterococcal infections who were treated with quinupristin/dalfopristin 7.5 mg/kg every 8 h for a mean duration of 12 days (range 2-52 days). Liver function tests, including a test for alkaline phosphatase, were performed before, during and after the end of therapy. All patients were followed for 1 month after completion of therapy.. Thirty-eight (68%) of the 56 patients responded. Myalgias/arthralgias were the leading adverse events occurring in 20 (36%) of the patients. Patients with myalgias/arthralgias had significantly higher levels of alkaline phosphatase (mean 318.7 IU/L) during the mid-term therapy cycle compared with patients without any joint or muscular pain (mean 216.3 IU/L, P = 0.05). In addition, 3/18 (16.6%) patients with myalgias/arthralgias had more than five-fold the normal levels of alkaline phosphatase, which did not occur in any of the other patients who did not develop myalgias/arthralgias (P = 0.04). All myalgias/arthralgias resolved after the discontinuation of quinupristin/dalfopristin. By univariate analysis, other factors associated with myalgias/arthralgias were relapse of haematological malignancy (P = 0.01), receiving tacrolimus within 1 month prior to treatment (P = 0.04) and receiving methotrexate during antimicrobial therapy (P = 0.05).. Myalgias/arthralgias occur frequently in cancer patients receiving quinupristin/dalfopristin and may be associated with biliary tract dysfunction, as measured by alkaline phosphatase or other factors that could lead to intra-hepatic cholestasis, such as relapse of haematological malignancy or treatment with tacrolimus or methotrexate.

Topics: Aged; Alkaline Phosphatase; Anti-Bacterial Agents; Antimetabolites, Antineoplastic; Antineoplastic Agents; Arthralgia; Biliary Tract Diseases; Enterococcus; Female; Gram-Positive Bacterial Infections; Humans; Immunosuppressive Agents; Liver Function Tests; Male; Methotrexate; Middle Aged; Muscular Diseases; Neoplasms; Pain; Recurrence; Risk Factors; Tacrolimus; Virginiamycin

Tacrolimus (FK506, Prograf) is marketed for the prophylaxis of organ rejection following allogenic liver or kidney transplantation. A previously conducted, randomized, 24-subject, crossover bioavailability study of 1 and 5 mg capsules (one period each) failed to demonstrate bioequivalence. A single-dose, four-period, four-sequence, randomized, crossover, replicate study (N = 32) was therefore used to evaluate the bioequivalence of the marketed 1 and 5 mg capsules in healthy volunteers. Tacrolimus blood concentrations were measured serially over 72 hours using a commercially available ELISA assay. Noncompartmental pharmacokinetic parameters were determined. Ninety percent CIs of log-transformed parameter ratios were 90.5-101.9, 87.1-101.7, and 89.7-103.8 for Cmax, AUC0-t, and AUC0-infinity, respectively. Since all values were within 80% to 125%, the capsules are bioequivalent. Based on %CVs, intersubject variability was approximately two to three times greater than intrasubject variability. The safety of single 5 mg oral tacrolimus doses administered to healthy volunteers at 7-day intervals was also ascertained.

Topics: Abdominal Pain; Adult; Area Under Curve; Arthralgia; Capsules; Cross-Over Studies; Diarrhea; Dose-Response Relationship, Drug; Female; Headache; Humans; Immunosuppressive Agents; Knee Joint; Male; Purpura; Tacrolimus; Therapeutic Equivalency

Multicentric reticulohistiocytosis (MRH) is a rare histiocytic disorder that involves the skin, joints, and visceral organs.. We report a 67-year-old woman with MRH who presented with a 2-years history of polyarthralgia and skin nodules. Her symptoms were an inflammatory polyarthropathy with punched-out lesions of the distal interphalangeal (DIP) joints of both hands. Doppler ultrasonography of the hands showed large bone erosions with power Doppler signals in the DIP joints. F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) demonstrated increased FDG uptake in cutaneous papules surrounding the affected joints, suggesting an inflammatory process. There was no evidence of malignancy. Biopsy samples of skin nodules exhibited dermal infiltration with CD68-positive histiocytes and multinucleated giant cells. The patient was diagnosed with MRH and treated with combination therapy comprising a steroid (prednisolone), tacrolimus, methotrexate, and infliximab, which resulted in clinical improvement. Following infliximab treatment, there was a significant decrease in a bone resorption marker (tartrate-resistant acid phosphatase 5b: TRACP-5b), suggesting that tumor necrosis factor-α targeting therapy may inhibit osteoclast formation and resorption activity in patients with MRH.. MRH is a progressive destructive arthritic condition, and early diagnostic and therapeutic strategies are necessary to improve the outcome. FDG-PET/CT and joint ultrasonography might be noninvasive imaging modalities that could help diagnose MRH.

Topics: Aged; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Antirheumatic Agents; Arthralgia; Asian People; Drug Combinations; Female; Fluorodeoxyglucose F18; Glucocorticoids; Hand; Histiocytes; Histiocytosis, Non-Langerhans-Cell; Humans; Immunosuppressive Agents; Infliximab; Methotrexate; Positron Emission Tomography Computed Tomography; Prednisolone; Skin; Tacrolimus; Treatment Outcome; Tumor Necrosis Factor-alpha; Ultrasonography, Doppler

Rheumatoid vasculitis is a rare, but most serious extra-articular complications of long-standing, seropositive rheumatoid arthritis (RA). Vasculitis of hepatic artery is an extremely rare but severe manifestation of rheumatoid vasculitis. A 72-year-old woman who presented with polyarthralgia for 2 months was diagnosed with early RA. Since she had manifestations of livedo reticularis, and liver dysfunction which was atypical for RA patients, a percutaneous needle liver biopsy was performed revealing arteritis of a medium-sized hepatic artery. Extensive investigations did not reveal evidences of other systemic causes such as malignancy or systemic vasculitis. The patient was diagnosed with rheumatoid vasculitis involving hepatic arteries based on Bacon and Scott criteria for rheumatoid vasculitis. With high dose corticosteroid and cyclophosphamide induction and methotrexate and tacrolimus maintenance treatment, she was successfully recovered. Association of rheumatoid vasculitis at very early stages of the disease may represent an early aggressive form of RA.

Topics: Adrenal Cortex Hormones; Aged; Arthralgia; Biopsy, Needle; Cyclophosphamide; Female; Hepatic Artery; Humans; Immunosuppressive Agents; Methotrexate; Rheumatoid Vasculitis; Tacrolimus

Topics: Adult; Amlodipine; Arthralgia; Calcineurin Inhibitors; Cystic Fibrosis; Humans; Immunosuppressive Agents; Lung Transplantation; Tacrolimus

Post-transplant distal limb bone marrow edema syndrome or calcineurin inhibitor-induced pain syndrome (CIPS) is generally a self-limiting but debilitating acute pain syndrome that has been reported in 2-14 % of renal transplant recipients. The disease is extensively described in the transplant literature in patients receiving the calcineurin inhibitors cyclosporine and tacrolimus. We present a case of CIPS arising in a patient 73 days after renal allograft, review the imaging findings, and discuss proposed etiologies and differential diagnoses. To the authors' knowledge, CIPS has not been characterized as a distinct entity in the radiology literature.

Topics: Adult; Arthralgia; Calcineurin Inhibitors; Diagnosis, Differential; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Multimodal Imaging; Premedication; Syndrome; Tacrolimus

Immunosuppressant-related hip pain can greatly affect a patient's mobility and increase the number of total hip arthroplasties. We investigated risk factors and causes of hip pain after orthotopic liver transplant.. The medical records of 175 adult orthotopic liver transplant patients, who were followed-up for more than 2 years, were retrospectively reviewed. Data collected from the records included primary disease, medications, biochemical results, Child-Turcotte-Pugh score, death, rejection, and complications related to liver transplant.. A total of 11 patients (6.3%) complained of hip pain, which was diagnosed as calcineurin-inhibitor-induced pain syndrome in 4 patients (2.3%), osteonecrosis of the femoral head in 3 patients (1.7%), and osteoporosis in 2 patients (1.1%). The incidence of calcineurin-inhibitor-induced pain syndrome was related to the dosage of tacrolimus (P > .05) but independent of methylprednisolone use. The occurrence of osteonecrosis of the femoral head was independent of the dosage and early withdrawal of methylprednisolone (P > .05). Patients with methylprednisolone withdrawal within 6 months had significantly longer survival than those using methylprednisolone for more than 6 months (50 ± 15 vs 41 ± 18 mo; P = .007).. Calcineurin-inhibitor-induced pain syndrome and osteonecrosis of the femoral head are main causes of hip pain in adult orthotopic liver transplant patients. Osteonecrosis of the femoral head was not common, but the incidence of hip pain owing to calcineurin-inhibitor-induced pain syndrome was relatively high in orthotopic liver transplant patients. Early withdrawal of methylprednisolone could benefit the patients' survival.

Topics: Adult; Aged; Arthralgia; Calcineurin Inhibitors; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Hip Joint; Humans; Immunosuppressive Agents; Incidence; Liver Cirrhosis; Liver Failure; Liver Transplantation; Male; Methylprednisolone; Middle Aged; Osteonecrosis; Osteoporosis; Retrospective Studies; Risk Factors; Tacrolimus