tacrolimus and Syndrome

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

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

A 52-year-old woman was admitted to our hospital with muscle pain and an elevated creatine kinase level. She had experienced wrist pain at onset seven years ago. The initial possible diagnoses were rheumatoid arthritis and adult-onset Still disease. The patient received corticosteroid and immunosuppressant therapy but experienced deterioration of symptoms. The symptoms of muscle pain and mild creatine kinase elevation emerged four years prior to her visit. Further elevation of creatine kinase was observed for three months before her visit despite adjusting the immunosuppressant dose. On admission, she presented with muscle moderate weakness of the trunk and extremities and pain of the shoulder and medial thigh muscles. Elevation of muscle enzymes and inflammatory response were also detected, and the anti-PL7 antibody was positive. Muscle biopsy from biceps brachii revealed necrotizing myopathy with necrotic and regenerated muscle fibers. The final diagnosis was anti-PL7 antibody positive myositis. The patient was treated with a higher dose of prednisolone and an adequate dose of tacrolimus. Following this treatment, the symptoms were improved. Anti-ARS (aminoacyl t-RNA synthetase) antibodies such as anti-PL7 antibody are useful in diagnosis and for prognostic prediction. Further investigation of patients with anti-ARS antibodies positive myositis is required.

Topics: Amino Acyl-tRNA Synthetases; Autoantibodies; Female; Humans; Middle Aged; Myositis; Syndrome; Tacrolimus

Netherton's syndrome (NS) is a rare autosomal recessive disease comprised of ichthyosis in the form of ichthyosis linearis circumflexa, hair shaft defects and atopic manifestations with an elevated IgE level. Various therapeutic options have been used in NS with variable success. Tacrolimus and pimecrolimus belong to the family of calcineurin inhibitors. They bind cytoplasmic proteins and the resulting complex binds calcineurin, inhibiting its ability to dephosphorylate the nuclear factor of activated T cells, thus suppressing gene transcription. There have been conflicting reports of the usefulness of tacrolimus in NS patients, with systemic absorption being the main adverse outcome. Here we report four Saudi siblings (two boys and two girls) with NS who were treated with topical tacrolimus and pimecrolimus with good control of their skin disease without any toxic effect. To our knowledge, this is the second report of the use of topical pimecrolimus in NS in the English literature.

Topics: Administration, Topical; Child; Child, Preschool; Dermatologic Agents; Drug Therapy, Combination; Female; Hair; Humans; Ichthyosis; Immunosuppressive Agents; Infant; Male; Remission Induction; Syndrome; Tacrolimus

Obliterative bronchiolitis (OB) or the clinical correlate bronchiolitis obliterans syndrome (BOS) is the main cause of late morbidity and mortality after heart-lung and lung transplantation. Although several risk factors for the development of OB/BOS have already been identified, very effective preventive therapy remains Utopian, although there has been much improvement in recent years. This paper attempts to summarize current experience in the medical treatment of OB/BOS, either by tackling the known risk factors for the development of OB/BOS or by changing the immunosuppressive drug regimen for treating established OB/BOS. The current treatment options, however, are rather anecdotal and mostly single-centre experiences. Therefore, multicentre studies are definitely needed to try to identify the most appropriate drug regimen either to prevent and to treat obliterative bronchiolitis/bronchiolitis obliterans syndrome.

Topics: Bronchiolitis Obliterans; Humans; Immunosuppressive Agents; Lung Transplantation; Mycophenolic Acid; Risk Factors; Syndrome; Tacrolimus

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

Chronic lung allograft dysfunction, which manifests as bronchiolitis obliterans syndrome (BOS), is recognized as the primary cause of morbidity and mortality after lung transplantation. In this study we assessed the efficacy and safety of two de novo immunosuppression protocols to prevent BOS.. Our study approach was a multicenter, prospective, randomized (1:1) open-label superiority investigation of de novo tacrolimus vs cyclosporine, with both study arms given mycophenolate mofetil and prednisolone after lung transplantation. Cytolytic induction therapy was not employed. Patients were stratified at entry for cystic fibrosis. Primary outcome was incidence of BOS 3 years after transplant (intention-to-treat analysis). Secondary outcomes were survival and incidence of acute rejection, infection and other adverse events.. Group demographic data were well matched: 110 of 124 tacrolimus vs 74 of 125 cyclosporine patients were treated per protocol (p < 0.01 by chi-square test). Cumulative incidence of BOS Grade ≥1 at 3 years was 11.6% (tacrolimus) vs 21.3% (cyclosporine) (cumulative incidence curves, p = 0.037 by Gray's test, pooled over strata). Univariate proportional sub-distribution hazards regression confirmed cyclosporine as a risk for BOS (HR 1.97, 95% CI 1.04 to 3.77, p = 0.039). Three-year cumulative incidence of acute rejection was 67.4% (tacrolimus) vs 74.9% (cyclosporine) (p = 0.118 by Gray's test). One- and 3-year survival rates were 84.6% and 78.7% (tacrolimus) vs 88.6% and 82.8% (cyclosporine) (p = 0.382 by log-rank test). Cumulative infection rates were similar (p = 0.91), but there was a trend toward new-onset renal failure with tacrolimus (p = 0.09).. Compared with cyclosporine, de novo tacrolimus use was found to be associated with a significantly reduced risk for BOS Grade ≥1 at 3 years despite a similar rate of acute rejection. However, no survival advantage was detected.

Topics: Adult; Bronchiolitis Obliterans; Cyclosporine; Female; Follow-Up Studies; Graft Rejection; Humans; Immunosuppressive Agents; Incidence; International Cooperation; Lung Transplantation; Male; Middle Aged; Outcome Assessment, Health Care; Prospective Studies; Risk Factors; Survival Rate; Syndrome; Tacrolimus; Treatment Outcome

Severe dermatitis, multiple allergies and metabolic wasting (SAM) syndrome is a recently recognized syndrome caused by mutations in the desmoglein 1 (DSG1) and desmoplakin (DSP) genes. Only two cases of SAM-DSP have been reported. We report on a 2-year-old girl presenting with pustular lakes within areas of erythema and large accumulations of intraepidermal neutrophils, which initially led to our misdiagnosis of generalized pustular psoriasis. No mutation was found in either the IL36RN or CARD14 genes by Sanger sequencing. The distinctive manifestations of erythroderma with severe itching, hypotrichosis, enamel defects, onychodystrophy, palmoplantar keratoderma and the crucial result of de novo missense mutation in exon 14 of the DSP gene (c.1828T>C, p.S610P) discovered by next-generation sequencing finally confirmed the diagnosis of SAM syndrome. The eruptions significantly improved after a 4-week treatment with oral acitretin and topical pimecrolimus. Oral gabapentin was prescribed simultaneously for 4 months, relieving her skin pruritus and suggesting that early treatment with pimecrolimus, acitretin and gabapentin for SAM-DSP syndrome is effective. It may even inhibit multiple allergies induced by skin barrier injury. In this work we also review the clinical features, differential diagnoses and pathological manifestations of SAM-DSP syndrome.

Topics: Acitretin; Administration, Cutaneous; Administration, Oral; Child, Preschool; Dermatitis, Exfoliative; Desmoplakins; Diagnosis, Differential; Diagnostic Errors; DNA Mutational Analysis; Female; Gabapentin; Humans; Hypersensitivity; Mutation, Missense; Psoriasis; Severity of Illness Index; Skin; Syndrome; Tacrolimus; Treatment Outcome; Wasting Syndrome

Reversible cerebral vasoconstriction syndrome (RCVS) is a cerebrovascular syndrome characterized by multi-segmental constrictions of the cerebral arteries that resolves spontaneously within 3 months. Although RCVS is considered to be due to transient dysregulation of vascular tone, the exact pathomechanism remains unclear. We describe the case of a 15-year-old girl with RCVS induced by tacrolimus, who developed generalized seizure during the postoperative course of orthotropic heart transplantation. Magnetic resonance imaging at symptom onset showed a few vasoconstrictions accompanying brain edema and convexity subarachnoid hemorrhage. Although her neurological conditions rapidly improved after discontinuing tacrolimus, a repeat magnetic resonance angiogram demonstrated delayed progression of the multi-segmental vasoconstrictions followed by subsequent resolution. Our case demonstrates that cautious observation of the cerebral arteries using magnetic resonance angiography and careful management of vasoconstrictions with vasodilators are necessary for delayed vasoconstrictions even when the clinical symptoms improve.

Topics: Adolescent; Brain Edema; Cerebral Angiography; Cerebral Arteries; Disease Progression; Electroencephalography; Female; Heart Transplantation; Humans; Immunosuppressive Agents; Magnetic Resonance Angiography; Multimodal Imaging; Seizures; Subarachnoid Hemorrhage; Syndrome; Tacrolimus; Time Factors; Tomography, X-Ray Computed; Vasoconstriction; Vasodilator Agents; Vasospasm, Intracranial

Topics: Blindness, Cortical; Blood Group Incompatibility; Calcineurin Inhibitors; Carcinoma, Hepatocellular; Confusion; Drug Substitution; Drug Therapy, Combination; Emergencies; Everolimus; Graft Rejection; Hepatitis B, Chronic; Humans; Immunosuppressive Agents; Liver Cirrhosis; Liver Neoplasms; Liver Transplantation; Male; Middle Aged; Photopheresis; Plasmapheresis; Sirolimus; Syndrome; 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

A 23-year-old woman was admitted with a relapse of ulcerative colitis. Tacrolimus therapy was initiated following inadequate response to corticosteroid therapy. Although the symptoms partially improved, she suddenly developed severe pain localized to the lower limbs on day 16 of tacrolimus therapy. By day 17, she was unable to move. Magnetic resonance imaging revealed born marrow edema in the lower limbs. We suspected calcineurin-inhibitor induced pain syndrome (CIPS) due to tacrolimus therapy. The pain improved within approximately four weeks of tacrolimus cessation. CIPS that is not associated with organ transplantation is a rare occurrence. Here we report a rare case of CIPS that was caused by tacrolimus therapy in a patient with ulcerative colitis.

Topics: Calcineurin Inhibitors; Colitis, Ulcerative; Female; Humans; Pain; Syndrome; Tacrolimus; Young Adult

Topics: Adolescent; Adult; Calcineurin Inhibitors; Cyclosporine; Female; Graft vs Host Disease; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Male; Middle Aged; Pain; Radiography; Retrospective Studies; Syndrome; Tacrolimus; Transplantation, Homologous

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

Leukoencephalopathy syndrome is a neurologic complication after organ transplantation caused predominantly by the neurotoxic effects of immunosuppressive agents on cerebral white matter. We determined the incidence and features of leukoencephalopathy syndrome in recipients after living-donor liver transplantations.. We retrospectively investigated 205 patients who had a living-donor liver transplantation performed at our institution between August 1998 and October 2008.. Leukoencephalopathy syndrome developed in 7 of 205 patients (3.9%) and in 4.7% of the 150 patients treated with tacrolimus-based immunosuppression after their living-donor liver transplantation. The underlying diseases were alcoholic cirrhosis in 3 cases, viral cirrhosis in 2, biliary atresia in 1, and Wilson disease in 1. Time to clinical onset after tacrolimus medication was 15.6 days (range, 6-30 days). The neurologic symptoms included headache, confusion, myoclonus, seizures, and visual disturbances. The mean serum trough level of tacrolimus at clinical onset was not very high (11.7 ng/mL [range, 6.0-14.2 ng/mL]). T2-weighted magnetic resonance imaging in all cases showed diffuse high signal in the white matter of the frontal, parieto-occipital, and temporal lobes. Treatment with antihypertensives, anticonvulsants, and withdrawal of tacrolimus resulted in amelioration of symptoms and magnetic resonance imaging abnormalities. Six patients showed complete recovery, while the seventh had residual rigidity and cognitive impairment caused by hypoxia during a convulsion.. Tacrolimus neurotoxicity can occur despite low trough levels; it depends on variations in pharmacokinetics, such as absorption and maximum concentration level. Early diagnosis and treatment of leukoencephalopathy syndrome should contribute to complete remission.

Topics: Anticonvulsants; Antihypertensive Agents; Biliary Atresia; Child; Contraindications; Female; Hepatolenticular Degeneration; Humans; Immunosuppressive Agents; Leukoencephalopathies; Liver Cirrhosis; Liver Transplantation; Living Donors; Male; Middle Aged; Postoperative Complications; Retrospective Studies; Syndrome; Tacrolimus; Treatment Outcome

Graft rejection and disease recurrence are well-recognized complications of liver transplantation (LT) for autoimmune hepatitis (AIH) and autoimmune sclerosing cholangitis (AISC). We describe indications and outcome of LT for childhood AIH and AISC.. Twenty-year retrospective review of a cohort of children (n = 101) with AIH, AISC, or AIH/sclerosing cholangitis overlap syndrome from a single center.. AIH type 1 (AIH1, n = 67) was more common than AIH type 2 (AIH2, n = 18), AISC (n = 8), or overlap syndrome (n = 8). Overall, 18 patients (18%) required LT, the indications being failure of medical therapy (n = 16) and fulminant liver failure (n = 2). Patients with AIH who required LT had a more prolonged prothrombin time at presentation compared with those who did not undergo transplantation (P = 0.01). Patients with AIH1 who received LT had a lower aspartate transaminase (P = 0.009) and alanine transaminase (P = 0.02) levels at initial diagnosis compared with those with AIH1 who did not undergo transplantation. Post-LT, 11 patients (61%) had 18 episodes of rejection, most were steroid sensitive. Disease recurrence was observed in 7 patients (39%, median duration post-LT 33 months), more common in AIH2 (80% recurrence rate), and those taking cyclosporine (71%, 5/7 patients) compared with those taking tacrolimus (18%, 2/11 patients; P < 0.05) and in 3 of 3 children who did not have maintenance steroids post-LT. The overall 5- and 7-year post-LT survival rate was 94% and 88%, respectively.. LT is a good therapeutic option for progressive AIH and AISC, although recurrence of the primary autoimmune process limits the outcome.

Topics: Alanine Transaminase; Aspartate Aminotransferases; Child; Cholangitis, Sclerosing; Cyclosporine; Female; Graft Rejection; Hepatitis, Autoimmune; Humans; Immunosuppressive Agents; Liver; Liver Failure, Acute; Liver Transplantation; Male; Prothrombin Time; Recurrence; Retrospective Studies; Steroids; Survival Analysis; Survival Rate; Syndrome; Tacrolimus; Treatment Outcome

Posterior reversible encephalopathy syndrome (PRES) is one of the serious adverse side effects of calcineurin inhibitors, which are used for the prophylaxis of graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (allo-SCT). We retrospectively analyzed 12 patients who developed PRES after allo-SCT aiming to clarify the clinical features, risk factors, and prognosis of PRES. Median onset of PRES is 17 days after allo-SCT. The most frequent primary symptom was high blood pressure, followed by headache and visual disturbance. Nine of our patients subsequently developed systemic seizure. Sites of PRES by MRI were detected in the frontal, temporal, and parietal lobes, basal ganglia, and brain stem in addition to occipital lobe. Serum creatinine that had increased two-fold from the baseline value was identified as the only risk factor for developing PRES after allo-SCT. The incidence of acute GVHD (grade II-IV) in patients with PRES and those without were 88.9% and 48.7%; respectively (P<0.001), and most of these patients died of GVHD or GVHD-related causes. The 2-year overall survival of patients with PRES and those without were 16.7% and 72.4%, respectively (P<0.001). These data suggested the importance of early intervention for PRES and exploitation of optimal GVHD prophylaxis after developing PRES.

Topics: Acute Disease; Adolescent; Adult; Calcineurin Inhibitors; Creatinine; Cyclosporine; Encephalitis; Female; Graft vs Host Disease; Humans; Immunosuppressive Agents; Male; Middle Aged; Prognosis; Retrospective Studies; Risk Factors; Stem Cell Transplantation; Syndrome; Tacrolimus; Transplantation, Homologous; Young Adult

A 45-year-old man with acute myelogenous leukemia (WHO classification, AML with multilineage dysplasia) received allogeneic bone marrow transplantation from an HLA-identical brother in first remission. He became febrile on day 7, and pulmonary failure and multi-organ failure developed subsequently, requiring mechanical ventilation. Chest X-ray and CT scan demonstrated diffuse interstitial shadows, suggesting the development of idiopathic pneumonia syndrome. Administration of methylprednisolone and tacrolimus was effective, but respiratory failure exacerbated along with a decrease in the dose of steroids. Lung biopsy revealed organizing pneumonia with CMV pneumonia. Methylprednisolone and mycophenolate mofetil were instituted, which led to an improvement of lung injury. Intensive immunosuppressive therapy with mechanical ventilation should be considered for the treatment of idiopathic pneumonia syndrome after allogeneic bone marrow transplantation.

Topics: Bone Marrow Transplantation; Drug Therapy, Combination; Humans; Idiopathic Interstitial Pneumonias; Immunosuppression Therapy; Immunosuppressive Agents; Leukemia, Myeloid, Acute; Male; Methylprednisolone; Middle Aged; Mycophenolic Acid; Respiration, Artificial; Syndrome; Tacrolimus; Transplantation, Homologous; Treatment Outcome

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

Topics: Brain Diseases; Female; Graft Rejection; Humans; Intensive Care Units; Liver Diseases; Liver Transplantation; Middle Aged; Syndrome; Tacrolimus

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

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

Topics: Anemia, Hemolytic, Autoimmune; Child; Cholangitis, Sclerosing; Cyclosporine; Humans; Immunosuppressive Agents; Liver Transplantation; Male; Purpura, Thrombocytopenic, Idiopathic; Splenectomy; Syndrome; Tacrolimus; Treatment Outcome

Calcineurin-inhibitor-induced pain syndrome (CIPS), a rare complication seen in patients with organ transplants, is associated with the use of calcineurin inhibitors (CIs) such as cyclosporine (CSP) and tacrolimus (FK). Patients with this syndrome usually present with severe leg pain. This case report demonstrates the successful pain control of this pain syndrome in a 42-year-old female patient who had been given CIs (FK and CSP) as an immunosuppressive agent after a bone marrow transplant. Twenty-one days after the transplantation, she complained of severe pain in her bilateral lower extremities; this lasted several weeks, and was resistant to ordinary analgesics such as intramuscular pentazocine, intravenous morphine, and even oral nifedipine, which is generally accepted as an effective analgesic agent for the pain in this syndrome. Due to the presence of allodynia, our patient's pain had neuropathic pain-like characteristics, unlike the pain in previously reported patients with other organ transplants. Her pain was successfully relieved by the administration of oral amytriptyline, clonazepam, oxycodone, and intravenous lidocaine, all of which ordinarily have an analgesic effect on neuropathic pain. CIPS in patients with hematopoietic stem cell transplants treated with FK may have a mechanism by which neuropathic pain may develop that is different from that in patients with other organ transplants.

Topics: Adult; Bone Marrow Transplantation; Calcineurin Inhibitors; Female; Humans; Immunosuppressive Agents; Leg; Pain; Pain Management; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Recurrence; Syndrome; Tacrolimus; Treatment Outcome

Topics: Adult; Brain; Brain Diseases; Edema; Female; Humans; Immunosuppressive Agents; Leukemia, Myeloid, Acute; Radiography; Stem Cell Transplantation; Syndrome; Tacrolimus; Treatment Outcome

Little is known about the effects of immunosuppression on patients with hereditary nonpolyposis colorectal cancer (HNPCC). We describe a kidney transplant recipient with unrecognized Muir-Torre syndrome in whom the administration of a tacrolimus-based regimen led to the eruption of multiple sebaceous tumors. The patient was later found to harbor an MSH2 mutation. Switching to a sirolimus-based regimen resulted in arrest of the disease. When the patient was switched back to tacrolimus, new facial lesions rapidly appeared. Switching again to sirolimus resulted again in halting the appearance of new lesions. This finding is in line with the known antiangiogenic activity of sirolimus and reports on the regression of cutaneous Kaposi's sarcoma in kidney transplant recipients switched from another immunosuppressive regimen to sirolimus. Further studies on the potential use of sirolimus for the treatment of de novo tumors in immunosuppressed kidney transplant recipients with HNPCC are warranted.

Topics: Adenoma; Colorectal Neoplasms, Hereditary Nonpolyposis; Disease Progression; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mutation; MutS Homolog 2 Protein; Sebaceous Gland Neoplasms; Sirolimus; Syndrome; Tacrolimus

We report on the efficacy of twice daily application of pimecrolimus 1 percent cream in a 48-year-old woman with reticular erythematous mucinosis (REM) syndrome and compare its results with pulsed dye laser (PDL) on the other side of her chest and back. The patient was previously treated by hydroxychloroquine but only a fair response was observed. After application of 5 months of pimecrolimus, the lesions completely resolved and the result was comparable with the other side of her body treated by pulsed dye laser PDL. Topical pimecrolimus and pulsed dye laser appear to be effective and safe treatments for REM.

Topics: Administration, Topical; Biopsy, Needle; Combined Modality Therapy; Erythema; Female; Follow-Up Studies; Humans; Immunohistochemistry; Low-Level Light Therapy; Middle Aged; Mucinoses; Syndrome; Tacrolimus; Treatment Outcome

Topics: Administration, Topical; Adult; Dermatitis, Exfoliative; Dermatologic Agents; Female; Hair; Humans; Ichthyosis, Lamellar; Syndrome; Tacrolimus

Omenn syndrome is a severe combined immunodeficiency with features of generalised erythroderma alopecia and evidence of Th2 inflammation (eosinophilia and raised IgE). We describe a differential effect of 2 calcineurin inhibitors, cyclosporine A (CsA) and tacrolimus, with CsA rapidly improving the erythroderma and lymphocytosis but tacrolimus having little effect.

Topics: Alopecia; Bone Marrow Transplantation; Calcineurin Inhibitors; Cyclosporine; Dermatitis, Exfoliative; Female; Hepatomegaly; Humans; Infant, Newborn; Lymphocytosis; Mothers; Severe Combined Immunodeficiency; Syndrome; Tacrolimus; Treatment Failure

Topics: Adult; Bone and Bones; Calcineurin Inhibitors; Cyclosporins; Everolimus; Follow-Up Studies; Humans; Immunosuppressive Agents; Kidney Transplantation; Magnetic Resonance Imaging; Male; Middle Aged; Osteoporosis; Pain; Postoperative Period; Radiography; Radionuclide Imaging; Sirolimus; Syndrome; Tacrolimus; Time Factors

Topics: Child; Dermatologic Agents; Humans; Ichthyosiform Erythroderma, Congenital; Immunosuppressive Agents; Male; Syndrome; Tacrolimus

Topics: Adolescent; Erythema; Humans; Immunosuppressive Agents; Male; Mucinoses; Syndrome; Tacrolimus

Topics: Child; Drug Resistance; Eosinophilia; Epstein-Barr Virus Infections; Herpesviridae Infections; Herpesvirus 6, Human; Humans; Immunosuppressive Agents; Intestines; Male; Syndrome; Tacrolimus

We report two renal transplant patients who experienced onset of severe bilateral knee pain 1 and 3 months after transplantation, respectively, while on tacrolimus therapy. Tacrolimus, like cyclosporine A, is an immunosuppressive agent that inactivates the enzyme calcineurin phosphatase. A bone pain syndrome was reported in 1989 in organ transplant recipients treated with cyclosporine A. Our cases suggest that tacrolimus may induce the same syndrome. Technetium 99m bone scanning shows increased uptake in the affected areas, and magnetic resonance imaging changes are consistent with bone marrow edema. The tacrolimus dosage need not be reduced unless trough levels are too high. The symptoms resolve completely within a few months. Imaging studies should be done to rule out avascular necrosis. The pathophysiology of this syndrome is discussed. Since tacrolimus was introduced recently, similar cases should be published.

Topics: Female; Follow-Up Studies; Humans; Kidney Failure, Chronic; Kidney Transplantation; Knee; Magnetic Resonance Imaging; Male; Middle Aged; Pain; Pain Measurement; Radionuclide Imaging; Risk Assessment; Syndrome; Tacrolimus; Technetium

Topics: Bone and Bones; Calcineurin Inhibitors; Foot; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Leg; Male; Middle Aged; Myelodysplastic Syndromes; Pain; Radionuclide Imaging; Shoulder; Syndrome; Tacrolimus; Transplantation, Homologous

A 66-year-old man developed a focal status epilepticus and left hemiparesis 4 days after an orthotopic liver transplantation and administration of FK 506. The magnetic resonance image revealed areas of increased signal on diffusion-weighted imaging (DWI) equally distributed to all vascular territories, most of which resolved completely within 2 weeks after discontinuation of FK 506. We conclude that DWI cannot reliably distinguish between reversible and irreversible lesions and that the presence of hyperintense lesions on DWI is not a definitive predictor of poor prognosis in reversible leukoencephalopathy patients.

Topics: Aged; Brain Edema; Diffusion Magnetic Resonance Imaging; Humans; Immunosuppressive Agents; Liver Transplantation; Male; Paresis; Status Epilepticus; Syndrome; Tacrolimus

The occurrence of a post-renal transplant syndrome of lower limbs joint pain has been reported extensively over the last decade. Clinical examination of the symptomatic joints is often unremarkable and magnetic resonance imaging reveals abnormalities of the bone marrow suggestive of edema and/or hemorrhage. The main striking features of this syndrome are the spontaneous resolution of the symptoms within a few weeks as well as of the marrow abnormalities. This syndrome has been attributed to cyclosporine, given in the immunosuppression regimen or to epiphyseal impactions. We here document the occurrence of this syndrome in 5 kidney graft recipients given a tacrolimus-based immunosuppression.

Topics: Adult; Female; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Knee Joint; Magnetic Resonance Imaging; Male; Middle Aged; Pain; Syndrome; Tacrolimus

Posterior Leukoencephalopathy Syndrome (PLES) is a rare but serious neurological condition with many aetiologies. In the era of organ transplantation there have been sporadic reports of calcineurin-inhibitor associated PLES. We describe a case, with subsequent uneventful retransplantation using sirolimus.

Topics: Brain Diseases; Calcineurin Inhibitors; Cyclosporine; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Magnetic Resonance Imaging; Male; Reoperation; Sirolimus; Syndrome; Tacrolimus

Topics: Adolescent; Alopecia; Amenorrhea; Autoantibodies; Autoimmune Diseases; Drug Therapy, Combination; Female; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Methylprednisolone; Prednisolone; Spasm; Syndrome; Tacrolimus

Neurotoxicity is a significant complication of the use of tacrolimus. From April 1998 to December 2001, we identified 10 patients (six women, four men) who developed 11 episodes of tacrolimus-associated posterior reversible encephalopathy syndrome (PRES) after allogeneic haematopoietic stem cell transplantation for haematological malignancies. The diagnosis was made by characteristic clinical findings (mental status changes, seizures, neurological deficits) with the exclusion of other causes and characteristic imaging findings. The median age was 35.5 years (range 19-57 years). Seven patients received a matched-unrelated donor transplant and three received a cord blood transplant. The overall incidence of PRES was 1.6%, while the incidence in matched-unrelated, mismatched-related and cord blood transplants was 3.5%, 4.9% and 7.1% respectively. Mental status changes, cognitive deficits, seizures and lethargy were the most common clinical findings. Eight of 10 patients had characteristic findings of hyperintensity of the white matter on T2-weighted images and FLAIR (fluid-attenuated inversion recovery) sequence on magnetic resonance imaging of the brain. Serum tacrolimus levels were within the therapeutic range in most patients. Tacrolimus treatment was continued (n = 4) or temporarily withheld (n = 7) for 1-14 d. One patient was changed to cyclosporine. In most patients, subsequent treatment with tacrolimus was well tolerated without recurrence of neurotoxicity.

Topics: Adult; Brain Diseases; Female; Follow-Up Studies; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Male; Middle Aged; Retrospective Studies; Syndrome; Tacrolimus; Treatment Outcome

Topics: Adult; Brain; Brain Diseases; Humans; Immunosuppressive Agents; Magnetic Resonance Imaging; Male; Syndrome; Tacrolimus

Topics: Adolescent; Female; Humans; Ichthyosiform Erythroderma, Congenital; Immunosuppressive Agents; Ointments; Skin Absorption; Syndrome; Tacrolimus

A 10-year old boy, the child of unrelated Bosnian parents presented with a superinfected ichthyotic erythroderma. The clinical features, histological findings and hair analysis led to the diagnosis of the autosomal-recessive inherited Comel-Netherton syndrome witch bacterial superinfection. Under careful therapy with small amounts of topical tacrolimus (Protopic 0.1% ), he improved and had longer disease-free intervals. Tacrolimus was administered intermittently and not during acute flares, thus avoiding systemic resorption even after long-time treatment despite the disturbed epidermal barrier in Comel-Netherton syndrome. Staphylococcus aureus producing enterotoxin C was isolated during flares which were sometimes accompanied by marked bacterial superinfection. It is possible, that this super antigen is involved in the observed aggravation of disease. The topical therapy with tacrolimus is an easy, flexible therapeutic option for this rare genodermatosis.

Topics: Anti-Bacterial Agents; Anti-Infective Agents, Local; Child; Hair; Humans; Ichthyosiform Erythroderma, Congenital; Immunosuppressive Agents; Male; Microscopy, Electron; Ointments; Skin; Staphylococcal Skin Infections; Staphylococcus aureus; Superantigens; Superinfection; Syndrome; Tacrolimus

Post-transplant complications are common among patients receiving immunosuppressive medications, including pain syndromes. Recently, a pain syndrome, calcineurin-inhibitor induced pain syndrome (CIPS) has been described. To our knowledge, this article is the second report of tacrolimus-associated CIPS, and the first report in the pediatric setting.

Topics: Adolescent; Humans; Immunosuppressive Agents; Liver Transplantation; Male; Neuralgia; Postoperative Complications; Syndrome; Tacrolimus

Bone pain after transplantation is a frequent complication that can be caused by several diseases. Treatment strategies depend on the correct diagnosis of the pain. Nine patients with severe pain in their feet, which was registered after transplantation, were investigated. Bone scans showed an increased tracer uptake of the foot bones. Magnetic resonance imaging demonstrated bone marrow oedema in the painful bones. Pain was not explained by other diseases causing foot pain, like reflex sympathetic dystrophy, polyneuropathy, Morton's neuralgia, gout, osteoporosis, avascular necrosis, intermittent claudication, orthopaedic foot deformities, stress fractures, and hyperparathyroidism. The reduction of cyclosporine- or tacrolimus trough levels and the administration of calcium channel blockers led to relief of pain. The Calcineurin-inhibitor Induced Pain Syndrome (CIPS) is a rare but severe side effect of cyclosporine or tacrolimus and is accurately diagnosed by its typical presentation, magnetic resonance imaging and bone scans. Incorrect diagnosis of the syndrome will lead to a significant reduction of life quality in patients suffering from CIPS.

Topics: Adult; Bone and Bones; Calcineurin Inhibitors; Cyclosporine; Enzyme Inhibitors; Female; Foot; Heart Transplantation; Humans; Kidney Transplantation; Magnetic Resonance Imaging; Male; Middle Aged; Organ Transplantation; Pain; Pain Management; Radionuclide Imaging; Syndrome; Tacrolimus

Tacrolimus is a macrolide immunosuppressant approved in oral and intravenous formulations for primary immunosuppression in liver and kidney transplantation. Topical 0.1% tacrolimus ointment has recently been shown to be effective in atopic dermatitis for children as young as 2 years of age, with minimal systemic absorption. We describe 3 patients treated with topical 0.1% tacrolimus who developed significant systemic absorption.. Three patients previously diagnosed as having Netherton syndrome were treated at different centers with 0.1% tacrolimus ointment twice daily. Two patients showed dramatic improvement. All patients were found to have tacrolimus blood levels within or above the established therapeutic trough range for oral tacrolimus in organ transplant recipients. None of these patients developed signs or symptoms of toxic effects of tacrolimus.. Patients with Netherton syndrome have a skin barrier dysfunction that puts them at risk for increased percutaneous absorption. The Food and Drug Administration recently approved 0.1% tacrolimus ointment for the treatment of atopic dermatitis. Children with Netherton syndrome may be misdiagnosed as having atopic dermatitis. These children are at risk for marked systemic absorption and associated toxic effects. If topical tacrolimus is used in this setting, monitoring of serum tacrolimus levels is essential.

Topics: Administration, Cutaneous; Child; Child, Preschool; Female; Humans; Ichthyosiform Erythroderma, Congenital; Immunosuppressive Agents; Male; Skin Absorption; Syndrome; Tacrolimus

We studied serial lung function in 11 patients with bronchiolitis obliterans syndrome who were treated with tacrolimus conversion following lung or heart-lung transplantation. Our results show that tacrolimus conversion slows the decline of lung function in bronchiolitis obliterans syndrome. The attenuation continues for at least 1 year following conversion.

Topics: Biopsy; Bronchi; Bronchiolitis Obliterans; Cyclosporine; Disease Progression; Follow-Up Studies; Forced Expiratory Volume; Heart-Lung Transplantation; Humans; Immunosuppressive Agents; Lung Transplantation; Maximal Midexpiratory Flow Rate; Retrospective Studies; Spirometry; Statistics, Nonparametric; Syndrome; Tacrolimus

Topics: Bone Diseases; Female; Humans; Immunosuppressive Agents; Kidney Transplantation; Leg Bones; Middle Aged; Pain; Syndrome; Tacrolimus

Topics: Adult; Azathioprine; Brain Diseases; Cyclosporine; Demyelinating Diseases; Drug Therapy, Combination; Family; Female; Humans; Immunosuppressive Agents; Liver Transplantation; Living Donors; Magnetic Resonance Imaging; Middle Aged; Prednisolone; Syndrome; Tacrolimus; Tomography, X-Ray Computed

Topics: Adult; Bone Transplantation; Brain; Brain Edema; Cyclosporine; Hodgkin Disease; Humans; Immunosuppressive Agents; Magnetic Resonance Imaging; Male; Syndrome; Tacrolimus

Topics: Adult; Biological Factors; Cell Movement; Humans; Leukocytes, Mononuclear; Male; Neutrophils; Pyoderma Gangrenosum; Syndrome; Tacrolimus

Topics: Female; Humans; Inflammation; Keratitis; Middle Aged; Syndrome; Tacrolimus; Vasculitis; Vestibular Diseases