tacrolimus and Fever

TAFRO syndrome is a systemic inflammatory disorder characterized by thrombocytopenia, anasarca, fever, reticulin fibrosis, renal dysfunction, and organomegaly. In contrast to that in multicentric Castleman disease, interleukin-6 targeting strategies seem ineffective in some TAFRO syndrome cases; however, the optimal treatment remains unclear. Here, we report 2 cases of TAFRO syndrome, where 1 with cardiomyopathy, successfully treated with tacrolimus. This is the first case report of successful treatment with tacrolimus in TAFRO syndrome.. Both patients (cases 1 and 2) developed fever, anasarca, thrombocytopenia, renal dysfunction, and mild hepatosplenomegaly.. In both patients, lymph node pathology revealed mixed type Castleman disease-like features, and bone marrow showed reticulin myelofibrosis. TAFRO syndrome was diagnosed based on the patients' laboratory, clinical, and pathologic findings. In case 2, we observed a rare complication of cardiomyopathy with no evidence of takotsubo cardiomyopathy or viral myocarditis.. In case 1, tocilizumab combined with glucocorticoids was ineffective and caused septic shock; additionally, cyclosporine A was discontinued because of hepatotoxicity. However, tacrolimus was effective in resolving TAFRO syndrome without any adverse events. In case 2, tacrolimus completely reversed TAFRO syndrome and was also effective in cardiomyopathy.. This report suggests that tacrolimus is potentially effective and safe as an initial treatment and a glucocorticoid-sparing agent. Our literature review shows that calcineurin inhibitors, including tacrolimus, may be effective in TAFRO syndrome. Since previous studies indicate a role of Th1 inflammation in TAFRO syndrome pathogenesis, tacrolimus may, therefore, be effective in treating TAFRO syndrome.

Topics: Adolescent; Aged; Bone Marrow; Calcineurin Inhibitors; Cardiomyopathies; Castleman Disease; Cyclosporine; Edema; Female; Fever; Fibrosis; Glucocorticoids; Hepatomegaly; Humans; Interleukin-6; Male; Primary Myelofibrosis; Renal Insufficiency; Splenomegaly; Syndrome; Tacrolimus; Thrombocytopenia; Treatment Outcome

High fevers and/or rashes prior to neutrophil engraftment are frequently observed after umbilical cord blood (UCB) transplantation, and the condition is referred to as pre-engraftment syndrome (PES). Few studies have evaluated the risk factors for and treatment response to PES. Therefore, we retrospectively characterized PES in 57 consecutive engrafted patients (≥ 12 years old) who received myeloablative dual UCB transplantation. All patients received TBI (≥ 13.2 Gy)-based myeloablative conditioning. Tacrolimus (n=35) or CYA (n=22) combined with mycophenolate mofetil was used as GVHD prophylaxis. PES was defined as the presence of non-infectious fever (≥ 38.5 °C) and/or rash prior to or on the day of neutrophil engraftment. The incidence (95% confidence interval) of PES was 77% (66-88%). The incidence of PES was significantly higher in patients who received CYA as a GVHD prophylaxis than those who received tacrolimus (P<0.001), and this association was confirmed in the multivariate analysis. The occurrence of PES did not impact OS or tumor relapse, although it may have increased non-relapse mortality (P=0.071). The incidence of acute GHVD or treatment-related mortality was not influenced by the choice to use corticosteroids to treat PES. This study suggests that use of CYA for GVHD prophylaxis increases the risk of PES following dual UCB transplantation.

Topics: Adolescent; Adult; Child; Cord Blood Stem Cell Transplantation; Female; Fever; Graft Survival; Graft vs Host Disease; Hematologic Neoplasms; Humans; Immunosuppressive Agents; Incidence; Male; Middle Aged; Mycophenolic Acid; Neutrophils; Risk Factors; Syndrome; Tacrolimus; Transplantation Conditioning

The safety and efficacy of a 1% cream formulation of pimecrolimus, a selective, nonsteroid immunomodulator, was studied in infants with atopic dermatitis (AD).. During a 6-week double-blind phase, 186 infants with mild/moderate AD were randomly assigned to twice-daily pimecrolimus cream 1% or vehicle. All patients were subsequently treated with open-label pimecrolimus for 20 weeks.. At the end of the double-blind phase, 54.5% and 23.8% of patients in the pimecrolimus and vehicle groups, respectively, were clear or almost clear of AD (P <.001). Similar improvements were observed in the Eczema Area and Severity Index, pruritus assessment, and the care giver's assessment. By the first return visit, 69.9% and 36.5% of pimecrolimus and vehicle-treated patients, respectively, achieved absent or mild pruritus. Efficacy during the double-blind phase was maintained throughout the open-label phase. Vehicle-treated patients transferring to open-label pimecrolimus rapidly achieved disease control comparable to those receiving continuous pimecrolimus. There were no significant differences between groups in application site reactions or skin infections. Most adverse events were mild or moderate and unrelated to treatment.. Pimecrolimus was safe in infants with AD, with rapid and sustained efficacy. Pimecrolimus holds promise as a valuable new treatment option for the youngest patients with AD.

Topics: Administration, Cutaneous; Analysis of Variance; Anti-Inflammatory Agents, Non-Steroidal; Dermatitis, Atopic; Dermatologic Agents; Diarrhea; Double-Blind Method; Female; Fever; Humans; Infant; Male; Ointments; Pharyngitis; Respiratory Tract Infections; Safety; Severity of Illness Index; Tacrolimus; Time Factors; Treatment Outcome

We conducted a prospective, randomized, double-blind study comparing amphotericin B colloidal dispersion (ABCD) with amphotericin B in the empirical treatment of fever and neutropenia. Patients with neutropenia and unresolved fever after > or = 3 days of empirical antibiotic therapy were stratified by age and concomitant use of cyclosporine or tacrolimus. Patients were then randomized to receive therapy with ABCD (4 mg/[kg.d]) or amphotericin B (0.8 mg/[kg.d]) for < or = 14 days. A total of 213 patients were enrolled, of whom 196 were evaluable for efficacy. Fifty percent of ABCD-treated patients and 43.2% of amphotericin B-treated patients had a therapeutic response (P = .31). Renal dysfunction was less likely to develop and occurred later in ABCD recipients than in amphotericin B recipients (P < .001 for both parameters). Infusion-related hypoxia and chills were more common in ABCD recipients than in amphotericin B recipients (P = .013 and P = .018, respectively). ABCD appeared comparable in efficacy with amphotericin B, and renal dysfunction associated with ABCD was significantly less than that associated with amphotericin B. However, infusion-related events were more common with ABCD treatment than with amphotericin B treatment.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Child; Child, Preschool; Colloids; Cyclosporine; Double-Blind Method; Female; Fever; Humans; Immunosuppressive Agents; Infant; Infusions, Intravenous; Kidney Function Tests; Male; Middle Aged; Mycoses; Neutropenia; Opportunistic Infections; Pilot Projects; Prospective Studies; Tacrolimus; Treatment Outcome

Coronavirus Disease 2019 (COVID-19) is currently a pandemic with a mortality rate of 1%-6% in the general population. However, the mortality rate seems to be significantly higher in elderly patients, especially those hospitalized with comorbidities, such as hypertension, diabetes, or coronary artery diseases. Because viral diseases may have atypical presentations in immunosuppressed patients, the course of the disease in the transplant patient population is unknown. Hence, the management of these patients with COVID-19 is an area of interest, and a unique approach is warranted. Here, we report the clinical features and our treatment approach for a kidney transplant patient with a diagnosis of COVID-19. We believe that screening protocols for SARS-Cov-2 should be re-evaluated in patients with solid-organ transplants.

Topics: Adult; Antiviral Agents; Betacoronavirus; Coronavirus Infections; Cough; COVID-19; COVID-19 Drug Treatment; Disease Management; Female; Fever; Glucocorticoids; Graft Rejection; Humans; Immunocompromised Host; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Lupus Nephritis; Oseltamivir; Pandemics; Pneumonia, Viral; Prednisone; SARS-CoV-2; Severity of Illness Index; Tacrolimus

Ehrlichiosis in lung transplant (LT) recipients is associated with severe outcomes. Ehrlichia ewingii is a less frequent cause of symptomatic ehrlichiosis, characterized by cytoplasmic inclusions (morulae) within circulating neutrophils. We report a case of E. ewingii infection in an LT recipient diagnosed promptly by blood smear exam and confirmed with molecular studies.

Topics: Aged; Animals; Anti-Bacterial Agents; Cytodiagnosis; Disease Transmission, Infectious; DNA, Bacterial; Doxycycline; Early Diagnosis; Ehrlichia; Ehrlichiosis; Female; Fever; Graft Rejection; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Ixodidae; Leukopenia; Lung Transplantation; Mycophenolic Acid; Neutrophils; Polymerase Chain Reaction; Prednisone; Tacrolimus; Thoracentesis; Thrombocytopenia; Tomography, X-Ray Computed

Nocardia thyroid abscess with pneumonia is a rare clinical presentation. We reported a liver transplant recipient with Nocardia thyroiditis and pneumonia after receiving high dose immunosuppressants to preserve his graft. The patient is a 50-year-old male who developed hepatitis C virus-related liver cirrhosis and received a liver transplant. Seven months post-transplantation the patient developed graft rejection, which was treated with 3 days pulse dose methyl-prednisolone followed by an increased dose of his tracolimus, mycophenolate and prednisolone. He presented to the hospital with a 2 week history of fever, tenderness in his anterior neck and dry cough. On admission his temperature was 39.5°C. The right wing of his thyroid gland was swollen to 3 cm in size, fluctuant and tender. On auscultation of his lungs there were fine crepitations and increased vocal resonance in the right middle lung field. On laboratory testing, a complete blood count (CBC) revealed leukocytosis (19,900/mm3) with neutrophils (97%). A chest X-ray showed an patchy infiltrates and round circumscribed densities in the superior segment of the right lower lobe of his lung. A CT scan of his neck revealed a diffusely enlarged right wing of the thyroid gland, 3.8 cm in diameter that had an abnormal hyposignal area. A CT of his chest revealed consolidation of the superior segment of the right lower lobe and necrotic right paratracheal lymph nodes with inflamed strap muscles. Fine needle aspiration of the right lobe of thyroid gland was performed. Modified acid-fast bacilli (MAFB) staining showed partially acid-fast beaded branching filamentous organisms and a culture grew out Nocardia asteroides. He was treated with trimethoprim-sulfamethoxazole for 6 months. He improved clinically and his chest X-ray also cleared.

Topics: Abscess; Fever; Graft Rejection; Humans; Immunosuppressive Agents; Liver Transplantation; Male; Middle Aged; Mycophenolic Acid; Nocardia Infections; Pneumonia, Bacterial; Prednisolone; Tacrolimus; Thyroiditis

Common pathogens of clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) are viruses, such as influenza virus. However, bacteria are rare pathogens for MERS. We report the first patient with MERS associated with febrile urinary tract infection. A 16-year-old lupus patient was admitted to our hospital. She had fever, headache, vomiting, and right back pain. Urinary analysis showed leukocyturia, and urinary culture identified Klebsiella pneumoniae. Cerebrospinal fluid examination and brain single-photon emission computed tomography showed no abnormalities. Therefore, she was diagnosed with febrile urinary tract infection. For further examinations, 99mTc-dimercaptosuccinic acid renal scintigraphy showed right cortical defects, and a voiding cystourethrogram demonstrated right vesicoureteral reflux (grade II). Therefore, she was diagnosed with right pyelonephritis. Although treatment with antibiotics administered intravenously improved the fever, laboratory findings, and right back pain, she had prolonged headaches, nausea, and vomiting. T2-weighted, diffusion-weighted, and fluid attenuated inversion recovery images in brain magnetic resonance imaging showed high intensity lesions in the splenium of the corpus callosum, which completely disappeared 1 week later. These results were compatible with MERS. To the best of our knowledge, our patient is the first patient who showed clinical features of MERS associated with febrile urinary tract infection.. In patients with pyelonephritis and an atypical clinical course, such as prolonged headache, nausea, vomiting, and neurological disorders, the possibility of MERS should be considered.

Topics: Adolescent; Encephalomyelitis; Female; Fever; Glucocorticoids; Humans; Immunosuppressive Agents; Kidney; Klebsiella Infections; Klebsiella pneumoniae; Magnetic Resonance Imaging; Prednisolone; Pyelonephritis; Radionuclide Imaging; Radiopharmaceuticals; Tacrolimus; Technetium Tc 99m Dimercaptosuccinic Acid; Urinary Tract Infections

We present a case report of visceral leishmaniasis in an elderly kidney transplant recipient (age, 73 years) with high intermittent fever in the 2 months before admission. Symptoms started 16 years after transplant. The patient received appropriate treatment with liposomal amphotericin and experienced transient increases in serum creatinine levels. Progression to dialysis was avoided with short duration of therapy (5 consecutive days, plus 1 more dose 1 week apart, a schedule alternative to 15-21 days [supported by the literature]) and a temporary reduction in tacrolimus exposure. After 4 months, recurrence of symptoms without other explanation required a second bone marrow aspirate; it revealed the persistence of amastigote forms. Visceral leishmaniasis is a potentially life-threatening infection; to the best of our knowledge, this is the oldest transplanted patient with a case of leishmaniasis described in the literature.

Topics: Acute Kidney Injury; Aged; Amphotericin B; Antiprotozoal Agents; Creatinine; Female; Fever; Humans; Kidney Transplantation; Leishmaniasis, Visceral; Liposomes; Male; Recurrence; Renal Dialysis; Tacrolimus; Transplant Recipients

Hemophagocytic syndrome (HPS) is an unusual disorder associated with systemic lupus erythematosus (SLE). A 64-year-old woman was admitted because of fever and urticarial vasculitis. Laboratory data revealed pancytopenia and immunological abnormalities, suggesting elevated disease activity. Prednisolone monotherapy failed to improve the pancytopenia despite the amelioration of other clinical findings. Because her condition was suggestive of HPS, tacrolimus at 2-3 mg/day was added to the prednisolone regimen. Eventually, the pancytopenia improved and prednisolone could be effectively tapered. Tacrolimus could be an additional or alternative modality for treating refractory HPS.

Topics: Bone Marrow; Dose-Response Relationship, Drug; Female; Fever; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Lymphohistiocytosis, Hemophagocytic; Middle Aged; Pancytopenia; Prednisolone; Remission Induction; Tacrolimus; Treatment Failure; Treatment Outcome; Urticaria; Vasculitis

We investigated clinical factors that affected the clearance of tacrolimus (FK506) administered by continuous drip infusion to children who had received allogeneic hematopoietic SCT. Blood FK506 levels were measured every day in 27 patients in an attempt to adjust the dose to maintain the target range (10-15 ng/mL). Patients who developed engraftment syndrome (ES) and acute GVHD and patients less than 7 years of age showed a higher FK506 clearance calculated from body weight (BW) for 5 or more consecutive days compared with the control groups. A time-course study showed that the occurrence of ES, but not acute GVHD, was related to increased clearance of FK506. When calculated from body surface area (BSA), a significant increase in FK506 clearance was observed in patients with ES, but not in those less than 7 years of age. FK506 clearance was not influenced by CYP3A5, multidrug resistance 1 or ABCG2 genotypes. None of the clinical parameters affected blood FK506 levels. Determination of the FK506 dose on the basis of frequent monitoring of the blood concentration seems to minimize the serious adverse effects induced by the immunosuppressant. It may be more accurate to dose FK506 according to BSA rather than BW for pediatric patients.

Topics: Adolescent; Aging; ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily B, Member 1; ATP Binding Cassette Transporter, Subfamily G, Member 2; ATP-Binding Cassette Transporters; Child; Child, Preschool; Cytochrome P-450 CYP3A; Drug Dosage Calculations; Erythema; Female; Fever; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Hypoxia; Immunosuppressive Agents; Infant; Male; Metabolic Clearance Rate; Neoplasm Proteins; Polymorphism, Genetic; Pulmonary Eosinophilia; Syndrome; Tacrolimus; Weight Gain

Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease that affects multiple organs. Neuropsychiatric SLE develops during the course of the disease in 50% to 74% of SLE patients. The pathogenesis of CNS manifestations is multifactorial. The most common neuropathological finding has, in various studies, been multifocal infarcts. The cerebral vascular lesions in SLE that can cause cerebral infarction can be categorized into thromboembolism and vasculitis. On the other hand, tacrolimus is an immunosuppressive drug used for several autoimmune diseases, which inhibits the calcineurin pathway in T cells and reduces accompanying inflammatory cytokine production. We experienced that treatment of a patient with SLE with tacrolimus and steroid pulse therapy yielded improvement of vasculitis of brain vessels on magnetic resonance angiography. We suggest that tacrolimus may play an important role in the treatment of vasculitis of SLE.

Topics: Adult; Brain; Calcineurin; Cerebrovascular Circulation; Female; Fever; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Magnetic Resonance Angiography; Magnetic Resonance Imaging; T-Lymphocytes; Tacrolimus; Treatment Outcome; Vasculitis

To document the clinical experience in the diagnosis and treatment of graft-versus-host disease(GVHD) after liver transplantation.. Clinical course was followed up and laboratory examinations were done in 3 patients with orthotopic liver transplantation (OLT) who developed acute GVHE. The diagnosis depended on clinical manifestations, skin biopsy, HLA typing and PCR short tandem repeat (PCR-STR). Immunosuppressive drugs were transferred and adjusted.. Fever, shin rash, diarrhea and pancytopenia were found within 3 to 8 weeks after liver transplantation. The liver function was normal. CMV antigen (pp65) and EBV antibody (IgM) were negative. The donor's HLA was detected in the host's peripheral blood cells. One female recipient had the donor's Y chromosome microchimerism detected by PCR-STR. All 3 patients died from infection, alimentary tract bleeding, or multiple organ failure in the end.. GVHD is not a rare complication easily misdiagnosed with pessimism out come after liver transplantation.

Topics: Cyclosporine; Erythema; Fatal Outcome; Female; Fever; Graft vs Host Disease; Humans; Immunosuppressive Agents; Liver Transplantation; Male; Middle Aged; Pancytopenia; Polymerase Chain Reaction; Prognosis; Skin; Tacrolimus

A case of gross skeletal muscle uptake of 18F-FDG during PET is described. The clinical context of immunosuppression after heart and lung transplantation and the absence of any other known association make the former a likely etiologic factor.

Topics: Adult; Diagnosis, Differential; Drug Interactions; Female; Fever; Fluorodeoxyglucose F18; Heart-Lung Transplantation; Humans; Immunosuppressive Agents; Lymphoma, B-Cell; Muscle, Skeletal; Mycophenolic Acid; Positron-Emission Tomography; Radiography, Thoracic; Radiopharmaceuticals; Tacrolimus; Tomography, X-Ray Computed

Topics: Acute Disease; Adult; Cyclosporine; Drug Therapy, Combination; Fever; Graft Rejection; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Kidney Transplantation; Male; Mycophenolic Acid; Tacrolimus