mycophenolic-acid and Fever

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

A 59-year-old woman sought treatment for 5 weeks of progressive exercise intolerance. At the time of presentation, dyspnea limited her ability to speak in complete sentences. She also reported new orthopnea. Her respiratory symptoms improved with rest and while standing. She endorsed associated intermittent low-grade fevers, cough productive of scant clear sputum, lower extremity swelling, bloating, weight loss, and reduced appetite. She had undergone two recent admissions with similar symptoms to other hospitals, during which she was treated empirically for community-acquired pneumonia and discharged after workups for infectious disease were unrevealing. She had a history notable for systemic lupus erythematosus (SLE) diagnosed in 2006, complicated by lupus nephritis in 2009. Most recently, her SLE had been quiescent while she was taking hydroxychloroquine (400 mg daily) and mycophenolate mofetil (MMF; 1 g twice daily). She reported baseline mild dyspnea with exertion since she received a diagnosis of SLE, but her symptoms had not previously affected her activities of daily living. The patient did not smoke, drink alcohol, or use recreational drugs, and her family history was unremarkable.

Topics: Activities of Daily Living; Dyspnea; Female; Fever; Humans; Lung Diseases; Lupus Erythematosus, Systemic; Lupus Nephritis; Middle Aged; Mycophenolic Acid

Late-onset neutropenia (LON) is an underrecognized complication of rituximab treatment. We undertook this study to describe its incidence, risk factors, clinical features, management, and recurrence.. We conducted a single-center retrospective cohort study of 738 adult patients with autoimmune disease who were treated with rituximab to induce continuous B cell depletion. The primary outcome measure was LON, defined as an unexplained absolute neutrophil count of <1,000 cells/µl during B cell depletion. Secondary outcome measures included incidental diagnosis, fever, sepsis, filgrastim use, and recurrent LON. We assessed predictors of LON using Cox proportional hazards regression models. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated.. We identified 107 episodes of LON in 71 patients. The cumulative incidence at 1 year of B cell depletion therapy was 6.6% (95% CI 5.0-8.7). The incidence rate during the first year was higher compared to thereafter (7.2 cases per 100 person-years [95% CI 5.4-9.6] versus 1.5 cases per 100 person-years [95% CI 1.0-2.3]). Systemic lupus erythematosus and combination therapy with cyclophosphamide were each independently associated with an increased risk of LON (adjusted HR 2.96 [95% CI 1.10-8.01] and 1.98 [95% CI 1.06-3.71], respectively). LON was not observed in minimal change disease or focal segmental glomerulosclerosis. The majority of episodes (59.4%) were asymptomatic. Fever and sepsis complicated 31.3% and 8.5% of episodes, respectively. Most patients (69%) were treated with filgrastim. Rituximab rechallenge occurred in 87% of patients, of whom 21% developed recurrent LON.. LON is common and often incidental. Most cases are reversible and respond well to filgrastim. However, LON can be associated with serious infections and thus warrants vigilant monitoring.

Topics: Adult; Aged; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Asymptomatic Diseases; Autoimmune Diseases; Azathioprine; Cyclophosphamide; Drug Therapy, Combination; Female; Fever; Filgrastim; Glomerulonephritis, Membranous; Glomerulosclerosis, Focal Segmental; Hematologic Agents; Humans; Immunologic Factors; Incidence; Lupus Erythematosus, Systemic; Male; Methotrexate; Middle Aged; Mycophenolic Acid; Nephrosis, Lipoid; Neutropenia; Proportional Hazards Models; Recurrence; Retrospective Studies; Risk Factors; Rituximab; Sepsis

Anti-Ku is a rare antibody which can be positive in some rheumatic diseases and it might be related to cardiac involvement. Polymyositis is an inflammatory myopathy, and its cardiac involvement seldom presents as myopericarditis and anti-Ku positive.. In this case, we report a mid-aged woman with chest pain, upper limbs weakness and fever unrelated with infection. The diagnosis of this case was unquestionably myopericarditis supported by ECG, cardiac MRI and negative findings in coronary arteries. Diagnosis of polymyositis was further clarified by the evidence of persistently increased CK, degeneration of proximal muscle in MRI, muscular dystrophy with lymphocytes infiltration in muscle biopsy. In the analysis of autoantibodies, we surprisingly discovered positive anti-Ku. Glucocorticoid and mycophenolate mofetil were then prescribed for polymyositis. Patient follow-up indicated remission of both myopericarditis and polymyositis. We finally clarified this rare case as a positive anti-Ku polymyositis with myopericarditis as cardiac involvement.. This report presents a rare case with anti-Ku positive polymyositis and the cardiac involvement of polymyositis was manifested as myopericarditis. Therefore, positive anti-Ku might explain the myopericarditis as cardiac involvement in polymyositis. More cases and longer duration of follow-up is required for the comprehensive understanding of the disease.

Topics: Autoantibodies; Chest Pain; Creatine Kinase; Electrocardiography; Female; Fever; Glucocorticoids; Humans; Ku Autoantigen; Magnetic Resonance Imaging; Middle Aged; Muscular Dystrophies; Mycophenolic Acid; Myocarditis; Polymyositis

Topics: Adult; Aged; Aged, 80 and over; Antirheumatic Agents; Azathioprine; Betacoronavirus; Clinical Laboratory Techniques; Cohort Studies; Coronavirus Infections; Cough; COVID-19; COVID-19 Testing; Cyclosporine; Diarrhea; Dysgeusia; Dyspnea; Fatigue; Female; Fever; Glucocorticoids; Humans; Hydroxychloroquine; Immunosuppressive Agents; Incidence; Intensive Care Units; Italy; Lupus Erythematosus, Systemic; Male; Methotrexate; Middle Aged; Mycophenolic Acid; Olfaction Disorders; Pandemics; Pneumonia, Viral; Prednisone; Respiratory Distress Syndrome; SARS-CoV-2; Telemedicine

Immunoglobulin (Ig)G4-related disease (IgG4-RD) is an unusual complication of systemic lupus erythematosus (SLE). We report a case in which belimumab proved efficacious for not only SLE, but also IgG4-RD. A 58-year-old Japanese woman had suffered from photodermatosis and erythema on the limbs for 20 years. She presented in slight fever and fatigue since 2016. Laboratory data showed hypergammaglobulinemia, proteinuria and positive results for anti-nuclear antibody and anti-double-stranded DNA antibody. Furthermore, elevated levels of serum IgG4 were detected. Contrast-enhanced computed tomography disclosed multiple areas of poor enhancement in the kidneys. The patient was diagnosed with lupus nephritis and IgG4-RD from renal biopsy. Treatment was started with prednisolone at 40 mg/day and mycophenolate mofetil. Proteinuria and serological findings improved initially, but tapering the dose of glucocorticoid proved difficult. After treatment was started with belimumab, clinical symptoms and proteinuria resolved completely. The dose of glucocorticoid was successfully tapered and serum concentration of IgG4 fell further. This appears to represent the first report of a case in which both SLE and IgG4-RD were effectively treated using belimumab.

Topics: Antibodies, Antinuclear; Antibodies, Monoclonal, Humanized; Female; Fever; Humans; Immunoglobulin G4-Related Disease; Immunosuppressive Agents; Kidney; Lupus Nephritis; Middle Aged; Mycophenolic Acid; Proteinuria; Tomography, X-Ray Computed

Inflammatory conditions manifest with a broad spectrum of signs and symptoms. Panniculitis is such a condition affecting the subcutaneous fat and presents as tender erythematous nodules. It is also associated with a systemic response and has been described in the literature as early as in 1892 by Pfeifer and in the 1920s by Weber and Christian. We present an unusual case of a Caucasian man with recurrent febrile illness, systemic inflammatory response and renal dysfunction requiring acute high dependency care. The authors successfully treated him with an antiproliferative agent, mycophenolate mofetil, which resulted in preventing him from having further episodes.

Topics: Aged; Diagnosis, Differential; Fever; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid; Panniculitis, Nodular Nonsuppurative; Syndrome

Systemic erythematosus lupus (SLE) affects multiple organs and involves complex immune dysfunction. Because vaccinations are inherently designed to stimulate the immune response, they have been linked with increased risk for flare of SLE and other autoimmune disorders, and their association with new-onset autoimmune disease has been postulated in several case reports. To our knowledge, this is the first reported case of the meningococcal vaccine precipitating SLE in a previously undiagnosed patient. We present a case of a previously healthy, 17 year old Asian female who presented to the ED with 14 days of fever and fatigue after administration of the meningococcal vaccine, as well as 5 days of facial rash. Initial labs showed pancytopenia, bandemia, proteinuria, elevated erythrocyte sedimentation rate, and elevated d-dimer. Both the antinuclear antibodies (ANA) and anti-double stranded DNA were positive and cervical lymphadenopathy was present. This case highlights the importance of considering acute autoimmune reactions such as SLE in the differential diagnosis when assessing previously healthy patients presenting with systemic symptoms such as fever and rash in the setting of recent vaccination.

Topics: Adolescent; Antibodies, Antinuclear; Diagnosis, Differential; Fatigue; Female; Fever; Fibrin Fibrinogen Degradation Products; Humans; Lupus Erythematosus, Systemic; Lymphadenopathy; Meningococcal Vaccines; Mycophenolic Acid; Prednisone; Vaccination

Hemophagocytic lymphohistiocytosis is an aggressive life-threatening syndrome of excessive immune activation. Hemophagocytic lymphohistiocytosis due to systemic lupus erythematosus is described as acute lupus hemophagocytic syndrome. Acute lupus hemophagocytic syndrome presenting with negative antinuclear antibody is uncommon.. A 57-year-old Sri Lankan woman presented with intermittent fever, weight loss, episodic confusion, and alopecia for 3 months. Investigations showed pancytopenia. Her erythrocyte sedimentation rate was 76 mm/hour and C-reactive protein was 2 mg/l. Septic screen was negative except for a positive sputum culture for Gram-negative coliforms. Chest X-ray was normal. Direct antiglobulin test was positive. Fever persisted with clinical worsening despite treatment with intravenous antibiotics. Antinuclear antibodies and double-stranded-deoxyribonucleic acid antibodies were negative. Bone marrow aspiration revealed features compatible with hemophagocytosis. Her serum ferritin and triglycerides were elevated. Diagnosis of hemophagocytic lymphohistiocytosis due to an evolving autoimmune disorder was made and she was treated with steroids. She showed a dramatic improvement and was discharged on oral steroids. After 6 months, while the steroids were being tapered she experienced oral ulcers, frothy urine, and ankle swelling and she was rehospitalized. Urine analysis revealed proteinuria with active sediment. Antinuclear antibodies and double-stranded-deoxyribonucleic acid antibodies were positive. Complement C3 and C4 were reduced. A renal biopsy revealed class IV-G lupus nephritis with immunofluorescence pattern consistent with systemic lupus erythematosus. Steroid dose was increased and mycophenolate mofetil was commenced. She improved.. This case showcases an uncommon presentation of acute lupus hemophagocytic syndrome with initial negative antinuclear antibody probably due to its cytokine-mediated pathogenesis. This is the first such reported case in South Asia to the best of our knowledge. According to the American College of Rheumatology criteria, our patient did not fulfill the criteria for systemic lupus erythematosus diagnosis for the initial hospitalization. But, according to the 2012 Systemic Lupus International Collaborating Clinics criteria, she did fulfill the criteria for systemic lupus erythematosus even in the first hospitalization which was subsequently proven with renal biopsy findings. This case confirms the increased sensitivity of Systemic Lupus International Collaborating Clinics criteria over American College of Rheumatology criteria in diagnosis of systemic lupus erythematosus.

Topics: Alopecia; Confusion; Female; Fever; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Lymphohistiocytosis, Hemophagocytic; Middle Aged; Mycophenolic Acid; Pancytopenia; Proteinuria; Steroids; Treatment Outcome; Weight Loss

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

Topics: Adult; Female; Fever; Humans; Immunocompromised Host; Lupus Erythematosus, Systemic; Lupus Nephritis; Muscle, Skeletal; Mycophenolic Acid; Prednisone; Prognosis; Pyomyositis; Tuberculosis; Venous Thrombosis

Topics: Adult; Cyclophosphamide; Cyclosporine; Female; Fever; Glucocorticoids; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Macrophage Activation Syndrome; Male; Middle Aged; Mycophenolic Acid; Retrospective Studies; Thrombocytopenia; Treatment Outcome

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

Here, we report on a patient after kidney transplantation, who developed fever and pneumonitis due to mycophenolic acid (MPA) treatment. Decreasing MPA dosages improved the symptoms, but after rechallenge with higher MPA doses the symptoms recurred. Discontinuation of MPA resulted in a complete resolution of fever within 24 h and a rapid improvement in pneumonitis. In vitro, the patient's polymorphonuclear neutrophils (PMNs) developed increased oxidative burst when incubated with MPA and N-formyl Met-Leu-Phe. We first report on MPA-induced pneumonitis and show that MPA can induce a pro-inflammatory response in kidney-transplanted patients. These pro-inflammatory changes might be due to paradoxical activation of PMNs.

Topics: Fever; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Mycophenolic Acid; Neutrophils; Pneumonia; Respiratory Burst; Tablets, Enteric-Coated

Topics: Autoimmune Lymphoproliferative Syndrome; Diagnosis, Differential; Diarrhea; Exanthema; Fever; Flow Cytometry; Hematologic Tests; Humans; Immunosuppressive Agents; Infant; Lymphocyte Count; Male; Mycophenolic Acid; Thrombocytopenia

Topics: Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Bacteremia; Central Nervous System Neoplasms; Drug Administration Schedule; Female; Fever; Fungemia; Humans; Immunocompromised Host; Immunosuppressive Agents; Lupus Nephritis; Lymphoma; Methotrexate; Mycophenolic Acid; Neurotoxicity Syndromes; Neutropenia; Rituximab; Treatment Outcome; Young Adult

Herein we have described the case of a male renal transplant recipient who developed drug fever apparently related to sirolimus. He had been stable under an immunosuppressive regimen of tacrolimus and mycophenolate mofetil, but developed acute cellular rejection at 5 years after transplantation due to noncompliance. Renal biopsy showed marked interstitial fibrosis, and immunosuppression was switched from mycophenolate to sirolimus, maintaining low tacrolimus levels. One month later he was admitted to our hospital for investigation of intermittently high fever, fatigue, myalgias, and diarrhea. Physical examination was unremarkable and drug levels were not increased. Lactic dehydrogenase and C-reactive protein were increased. The blood cell count and chest radiographic findings were normal. After extensive cultures, he was started on broad-spectrum antibiotics. Inflammatory markers and fever worsened, but diarrhea resolved. All serologic and imaging tests excluded infection, immune-mediated diseases, and malignancy. After 12 days antibiotics were stopped as no clinical improvement was achieved. Drug fever was suspected; sirolimus was replaced by mycophenolate mofetil. Fever and other symptoms disappeared after 24 hours; inflammatory markers normalized in a few days. After 1 month the patient was in good health with stable renal function. Although infrequent, the recognition of drug fever as a potential side effect of sirolimus may avoid unnecessary invasive diagnostic procedures. Nevertheless, exclusion of other common causes of fever is essential.

Topics: Fever; Glomerulonephritis, IGA; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Prednisone; Radiography, Thoracic; Sirolimus; Treatment Outcome

Mycophenolate mofetil (MMF) is increasingly used to prevent acute and chronic rejection following kidney transplantation and in autoimmune diseases. Here, we report on a patient after kidney transplantation, who developed an acute inflammatory syndrome characterized by fever and oligoarthritis within 1 week after increasing the MMF dosage. MMF was discontinued resulting in a complete resolution of the syndrome within 48 h. We demonstrated in vitro that the patient's phorbol myristate acetate (PMA-) and formyl Met-Leu-Phe (fMLP-) stimulated polymorphonuclear neutrophils (PMNs) developed increased oxidative burst when incubated with MMF. This report demonstrates that MMF can also induce acute inflammatory syndrome in patients following kidney transplantation and that this syndrome might be due to a paradox, pro-inflammatory reaction of PMNs.

Topics: Aged; Ankle Joint; Arthritis; Fever; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Mycophenolic Acid; N-Formylmethionine Leucyl-Phenylalanine; Neutrophils; Respiratory Burst; Syndrome; Tetradecanoylphorbol Acetate

Calcineurin inhibitors are one of the most common drugs used for prevention of acute rejection in recipients of renal allografts. New immunosuppressors have reduced the incidence of acute renal allograft rejection. There have been numerous recent attempts to develop alternative patterns of immunosuppressors for prevention of chronic renal allograft failure, and enhancing its survival. We described a patient who developed numerous complications after the initial postransplant period. He was treated with a calcineurin inhibitors-free immunosuppression in order to avoid nephrotoxicity, but had over 30 ng/ml of sirolimus. Renal function was impaired after cyclosponne withdrawal. Sirolimus was used in association with mycofenolate mofetil and prednisone.

Topics: Adult; Calcineurin Inhibitors; Comorbidity; Cyclosporine; Drug Therapy, Combination; Fever; Glomerulosclerosis, Focal Segmental; Humans; Immunosuppressive Agents; Kidney Diseases; Kidney Transplantation; Male; Mycophenolic Acid; Prednisone; Pyelonephritis; Recurrence; Sirolimus; Ureteral Diseases; Urinary Bladder Fistula; Urinary Fistula

Aspergillus infection is a rare but devastating complication following organ transplantation with high mortality rate. Aspergillus fumigatus is the most common cause of invasive aspergillosis. This fungus is present in the environment worldwide. Aspergillus infection is mainly acquired by inhalation of spores and several nosocomial infections in transplant recipient have been associated with construction work at hospitals. Risk factors for invasive aspergillosis include administration of steroid boluses, history of cytomegalovirus infection, neutropenia and prolonged antibiotic use after transplantation. Successful treatment depends on three factors: early diagnosis, aggressive antifungal therapy and decrease or removal of immunosuppression. Amphotericin deoxycholate has been the standard treatment for many years but lipid preparations for amphotericin are now used due to their significantly fewer adverse effects. A number of new antifungal drugs are now being developed including new azoles such as voriconazol and echinocandin. Invasive aspergillosis has a high mortality rate more than 95% when cerebral dissemination is demonstrated. We report the case of a 47 years old woman who received a cadaveric renal graft and developed pulmonary aspergillosis with fulminant cerebral dissemination two months later. The diagnosis of pulmonary aspergillosis was by culture isolation obtained from bronchioalveolar lavage. Removal of immunosuppresive agents and liposomal amphotericin B therapy were started shortly after admission. Brain CT scan performed on the 12th day showed cerebral dissemination. The recipient died two days later. Our patient had several risk factors such as the administration of steroid boluses and cytomegalovirus infection. Invasive aspergillosis must be always included in the differential diagnosis of fever and pulmonary disease in the renal transplant recipient.

Topics: Amphotericin B; Aspergillosis; Aspergillus fumigatus; Cross Infection; Cyclosporine; Cytomegalovirus Infections; Fatal Outcome; Female; Fever; Humans; Immunocompromised Host; Immunosuppressive Agents; Kidney Transplantation; Liposomes; Lung Diseases, Fungal; Middle Aged; Mycophenolic Acid; Neuroaspergillosis; Neutropenia; Polycystic Kidney, Autosomal Dominant; Prednisone; Risk Factors

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

Mycophenolate mofetil (MMF) is increasingly used for prevention of allograft rejection and to treat immune disorders. We report the development of an acute inflammatory syndrome in two patients with Wegener's granulomatosis after MMF was introduced, because of persistent renal and systemic disease activity despite cyclophosphamide treatment. Within 1 week both patients developed an acute inflammatory syndrome, characterized by fever, arthralgias and muscle pain. No infection could be detected and no indications for increased Wegener's activity were present. MMF was stopped resulting in a rapid and complete resolution of the syndrome. A rechallenge with 2 g of MMF in the second patient resulted in a relapse of the syndrome within 4 days. There was an association between symptoms and increased levels of mycophenolic acid (MPA) acyl glucuronide and serum interleukin-6, suggesting the induction of inflammatory cytokines by MPA acyl glucuronide as the cause of the syndrome. Therefore, special attention should be given to side effects such as fever, arthralgias and muscle pain when treating patients with Wegener's granulomatosis during the active phase. Because this side effect of MMF may also occur after solid organ transplantation and in other immune disorders, pharmacokinetic profiling of MPA and MPA acyl glucuronide is needed in future studies with MMF.

Topics: Acute Disease; Arthralgia; Female; Fever; Granulomatosis with Polyangiitis; Humans; Immunosuppressive Agents; Inflammation; Male; Middle Aged; Muscles; Mycophenolic Acid; Pain; Syndrome

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