mycophenolic-acid and Syndrome

Topics: Anti-Bacterial Agents; Azathioprine; Glucocorticoids; Humans; Immunosuppressive Agents; Infliximab; Liver Abscess; Male; Middle Aged; Mycophenolic Acid; Prednisone; Syndrome; Tumor Necrosis Factor-alpha

Mycophenolate mofetil (MMF) and mizoribine (MZR) are increasingly used as immunosuppressive agents for organ transplantation and chronic inflammation. We report a patient with rheumatoid arthritis who had an acute inflammatory syndrome triggered by preoperative immunosuppression therapy with both MMF and MZR.. A 41-year-old woman with IgA nephropathy was referred to our department for living donor renal transplantation. She had rheumatoid arthritis that was adequately treated with prednisolone 5 mg once a day and salazosulfapyridine 2000 mg once a day. MMF 1000 mg twice a day was started for desensitization therapy. Three days later, the patient developed arthritis in the joints of her left hand and elevated inflammatory markers. On day 7, MMF was switched to MZR 150 mg 3 times a day. However, the symptoms extended to both shoulders and the joints of the right foot; MZR was discontinued. The arthritis and inflammatory markers improved. Two months later, the patient was rechallenged with MMF followed by MZR, resulting in a similar clinical course as previously. Tacrolimus (TAC) 3 mg twice a day and everolimus (EVL) 0.5 mg twice a day were introduced as alternative immunosuppressant therapies. No arthritis occurred. ABO-compatible living donor renal transplantation was successfully performed. The patient received TAC, EVL, prednisolone, rituximab, and basiliximab, and her postoperative course was uneventful without arthritis or rejection. At 9 months postoperatively, the serum creatinine was 0.79 mg/dL.. Acute inflammatory syndrome is an extremely rare complication triggered by preoperative immunosuppression therapy. If antimetabolites cannot be used in immunologically high-risk patients, transplantation becomes very difficult. Clinicians should keep in mind this paradoxical reaction.

Topics: Adult; Arthritis; Female; Graft Rejection; Humans; Immunosuppressive Agents; Inflammation; Kidney Transplantation; Mycophenolic Acid; Ribonucleosides; Syndrome

Lichen planopilaris (LPP), a follicular form of lichen planus, is a rare inflammatory lymphocyte mediated disorder. Although the physiopathology is unclear, an autoimmune etiology is generally accepted. Women are affected more than men, and the typical age of onset is between 40 and 60 years. LLP is a primary cicatricial alopecia whose diagnosis is supported in the early stage by both clinical and histopathological findings. Within the margins of the expanding areas of perifollicular violaceous erythema and acuminate keratotic plugs, the histology can show the lichenoid perifollicular inflammation. LPP can be subdivided into 3 variants: classic LPP, frontal fibrosing alopecia (FFA), and Lassueur Graham-Little Piccardi syndrome. With the exception of FFA, the hairless patches of the scalp can be unique or can occur in multiples and can present with a reticular pattern or as large areas of scarring. This condition can have major psychological consequences for the affected patients. The therapeutic management often is quite challenging, as relapses are common after local or systemic treatments. Further research is needed on the pathogenesis, and randomized controlled trials of treatment with scientific evaluation of the results are necessary to appreciate the proposed treatment.

Topics: Administration, Topical; Adrenal Cortex Hormones; Adult; Alopecia Areata; Anti-Inflammatory Agents; Diagnosis, Differential; Female; Humans; Lichen Planus; Male; Middle Aged; Mycophenolic Acid; Recurrence; Scalp Dermatoses; Syndrome

Evans syndrome is a rare disorder characterized by combined autoimmune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA). Standard treatments consist of transfusions, corticosteroids, splenectomy, IVIG, anabolic steroids, vincristine, alkylating agents, or cyclosporine. In a patient with refractory disease, an allogeneic hematopoietic stem cell transplant (HSCT) resulted in complete clinical and serologic remission for more than 30 months. Allogeneic HSCT may be the only current curative therapy for Evans syndrome but may also be complicated by significant toxicities.

Topics: Adrenal Cortex Hormones; Adult; Anemia, Hemolytic, Autoimmune; Antibodies, Monoclonal; Autoimmune Diseases; Combined Modality Therapy; Danazol; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Infliximab; Male; Mycophenolic Acid; Opportunistic Infections; Prednisone; Purpura, Thrombotic Thrombocytopenic; Remission Induction; Salvage Therapy; Splenectomy; Syndrome; Thrombocytopenia; Transplantation Conditioning; Transplantation, Homologous; Vincristine

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

Bronchiolitis obliterans syndrome (BOS) is the major problem after lung and heart-lung transplantation (LTx/HLTx). Sirolimus (Sir) and Mycophenolate (MMF) showed a promising efficacy in the treatment of BOS in animal models. The first clinical experience in converting LTx/HLTx-recipients with BOS from calcineurin inhibitor-(CNI)-based immunosuppression to a Sir-MMF based immunosuppression is reported herein.. Six LTx- and five HLTx-recipients (eight men; 0.9 to 8 years after transplantation) with CNI-based immunosuppression (plus MMF) in whom BOS was diagnosed were included in the study. Mean patient age was 37+/-13 years (range 17-62 years). Sir was started with 6 mg and continued adjusted to according target trough levels (8-14 ng/ml). Subsequently, the CNIs were tapered down and finally stopped. Follow up included self determined pulmonary function tests, microbiological screening, chest radiographs, and laboratory studies. Two acute rejection episodes occurred during the study period. The incidence of infection was 2.2+/-1.3 infections/patient-year after conversion. Mean FEV1 decreased after a mean follow up of 14.8+/-1.4 months: from 2.1+/-0.7 l prior conversion to 1.3+/-0.6l after conversion (P=0.03). However, graft function remained stable in three patients and progression of BOS slowed down in three patients. Overall, 2 of 10 patients died due to ongoing BOS while awaiting retransplantation. After BOS was diagnosed, conversion to MMF and Sir stabilized graft function only in some of the converted patients. Therefore, earlier administration of Sir-based immunosuppression might be a more promising approach. Whether conversion to CNI-free immunosuppression can actually ameliorate the extent or progression of BOS has to be investigated in randomized trials.

Topics: Adolescent; Adult; Bronchiolitis Obliterans; Calcineurin Inhibitors; Disease Progression; Female; Graft Rejection; Heart-Lung Transplantation; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney; Lung Transplantation; Male; Middle Aged; Mycophenolic Acid; Sirolimus; Syndrome

There are no data on the effects of mycophenolate mofetil (MMF) on the incidence of bronchiolitis obliterans syndrome (BOS) in lung-transplant patients. This study attempted to determine whether MMF reduces the incidence of BOS in de novo lung transplant recipients compared with azathioprine (AZA).. This prospective, randomized, open-label, multicenter study compared the effects of MMF with AZA in combination with induction therapy, cyclosporine (Neoral) and corticosteroids in patients receiving their first lung transplant. Primary endpoint was incidence of BOS at 3 years. Secondary endpoints were incidence of acute rejection, time to first rejection event, and survival.. The incidence of acute rejection and the time to first rejection event at 1 and 3 years did not differ between groups (54.1% vs. 53.8% and 56.6% vs. 60.3% for MMF and AZA respectively). Survival at 1 year tended to be better in patients receiving MMF (88 vs. 80%, P = 0.07). At year 3, there was no difference in survival or in the incidence, severity or time to acquisition of BOS between the two groups. Treatment was generally well tolerated, however more patients withdrew from AZA treatment than from MMF (59.6% vs. 46.5%, P = 0.02). As a result, there was an imbalance in the observation times of the two groups (876 +/- 395 vs. 947 +/- 326 days).. No differences were seen in the incidence of acute rejection or BOS in lung transplant recipients treated with MMF or AZA. This null result may have been influenced by the shorter observation time for AZA patients.

Topics: Adolescent; Adult; Aged; Azathioprine; Bronchiolitis Obliterans; Drug Therapy, Combination; Graft Rejection; Humans; Immunosuppressive Agents; Lung Transplantation; Middle Aged; Mycophenolic Acid; Prospective Studies; Syndrome

A 9-year-old castrated male poodle dog was presented with icterus, anorexia, and lethargy. The dog was diagnosed with hypothyroidism 1 month before and was treated with levothyroxine. Severe anaemia with spherocytes, positive saline agglutination test, and hyperbilirubinemia indicated immune-mediated haemolytic anaemia (IMHA). Therefore, immunosuppressive therapy with prednisolone, mycophenolate mofetil, and danazol was started. Although the IMHA was well controlled, during tapering of prednisolone, acute multiple joint swelling and oedema suspected immune-mediated polyarthritis occurred twice. First, clinical symptoms improved as the dosage of prednisolone increased. However, the dog showed severe adverse effects to the steroid. Second time, we added leflunomide as another immunosuppressant, and clinical signs of arthritis disappeared. About 3 weeks later, despite the immunosuppressive therapy, skin lesions resembling an autoimmune dermatologic disorder spread throughout the body. Addition of cyclosporine resolved the skin lesions. This is a case report of a dog showing several sporadic clinical signs related to multiple autoimmune syndromes and their management using different immunosuppressant drugs.

Topics: Anemia, Hemolytic, Autoimmune; Animals; Dog Diseases; Dogs; Immunosuppressive Agents; Male; Mycophenolic Acid; Prednisolone; Syndrome

The peculiar presentation of overlap syndrome in children makes precise diagnosis difficult. Children with overlap syndrome may or may not have specific antibodies. We present the case of a 12-year-old girl diagnosed with overlap syndrome of systemic lupus erythematosus (SLE) and juvenile polymyositis (JPM) who tested positive for anti-OJ antibodies.. We describe the case of a 12-year-old girl diagnosed with SLE at the age of 7 and presented with fever with malar rash, periungual erythema, generalized weakness, and multiple joint pain at admission. The patient had persistent joint pain and weakness after intravenous methylprednisolone administration and complained of an inability to walk with a positive test for Gower's sign one week after admission, accompanied by elevated alanine aminotransferase (ALT) and creatine-phospho-kinase (CPK) levels. The results of nerve conduction velocity test were normal. Electromyography revealed abundant spontaneous activity and myopathic motor unit action potentials in the right deltoid, biceps, and iliopsoas, in addition to fibrillation and mild myopathic motor unit action potentials in the right rectus femoris muscle. Magnetic resonance imaging revealed diffusely increased signal intensities in the myofascial planes of the bilateral iliopsoas, gluteus, obturator, pectineus, and hamstring muscles. Anti-nuclear antibody, anti-RNP, and rheumatoid factor IgG tests were positive, and inflammatory myopathy autoantibodies revealed anti-OJ antibody positivity, which strongly indicated autoimmune myositis. High-resolution computed tomography of the lung revealed mild pericardial effusion without any evidence of interstitial lung disease. We initiated intravenous pulses of methylprednisolone treatment, followed by cyclosporine, mycophenolate mofetil, and oral steroids. Clinical improvement with a delayed, slowly reduced CPK level after the above treatment and she was discharged after the 18th day of hospitalization.. Overlap syndrome with inflammatory myositis can occur years later in pediatric SLE cases. We should be alert when patients with SLE develop a new presentation characterized by decreased SLE-specific autoantibody titers, positive anti-RNP antibodies, and elevated CPK. Treatment of the overlap syndrome of SLE and JPM is individualized, and the course differs between pediatric and adult patients.

Topics: Adult; Alanine Transaminase; Antibodies, Antinuclear; Arthralgia; Autoantibodies; Child; Creatine; Cyclosporins; Female; Humans; Immunoglobulin G; Lupus Erythematosus, Systemic; Methylprednisolone; Mycophenolic Acid; Myositis; Polymyositis; Rheumatoid Factor; Syndrome

Topics: Bronchiolitis; Child; Coatomer Protein; Glucocorticoids; Humans; Hydroxychloroquine; Immunosuppressive Agents; Male; Mutation, Missense; Mycophenolic Acid; Prednisolone; Syndrome

Cyclosporine (CSA) is an alternative treatment for autoimmune hepatitis (AIH), however, its unknown long-term safety and efficacy have limited its use.. Examine the long-term outcome of children and young adults with AIH treated with CSA for at least 4 years.. Twenty patients were included in this retrospective study: 15 with classical AIH and 5 with autoimmune hepatitis/autoimmune sclerosing cholangitis overlap syndrome (ASC). CSA was administered as first (12 patients) or second-line (8 patients) treatment, alone or in combination with azathioprine or mycophenolate mofetil and/or prednisone.. CSA determined initial clinical and biochemical remission in all patients. At the end of follow-up (median 8.6; range 4-20.4 years), all patients are alive with their native liver; 15 in complete remission (75%), 2 with incomplete response to treatment and 3 listed for liver transplant. Side effects were mild and transitory after dose tapering or, in 1 case, after CSA withdrawal. Hypertrichosis and moderate gingival hyperplasia were the most frequent. Two patients presented mild transient glomerular filtration rate (GFR) reduction. Median GFR at the beginning and end of treatment was not statistically different for all patients.. CSA was effective and safe in the long-term treatment of our cohort of patients with AIH, tailoring the treatment remains key-points during CSA administration.

Topics: Adolescent; Azathioprine; Child; Child, Preschool; Cholangitis, Sclerosing; Cyclosporine; Drug Therapy, Combination; Female; Follow-Up Studies; Hepatitis, Autoimmune; Humans; Immunosuppressive Agents; Liver Transplantation; Male; Mycophenolic Acid; Prednisone; Remission Induction; Retrospective Studies; Syndrome; Time Factors; Treatment Outcome

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

Hypocomplementemic urticarial vasculitis syndrome (HUVS) is a rare autoimmune disease characterized by multiple organ system involvement, including renal disease, with low complement levels. We report the case of a 31-year-old woman who presented with nonspecific symptoms including fatigue, diarrhea, macular rash and abdominal pain with acute renal failure leading to end-stage kidney disease. Laboratory results showed hematuria, nephrotic range proteinuria, worsening creatinine and low C1q levels. Left kidney biopsy showed proliferative glomerulonephritis with crescent formation. She was treated with 6 months of intravenous cyclophosphamide, followed by 2 doses of intravenous rituximab (1g each), thereafter maintained on mycophenolate mofetil and glucocorticoid-based therapy. She experienced a full recovery of renal function after 12 months of dialysis dependence. Hypocomplementemic urticarial vasculitis syndrome with crescentic glomerulonephritis is a rare disease with only 5 other reported cases in literature. In our case, we document a delayed but excellent renal recovery during a 2-year follow-up.

Topics: Adult; Complement C1q; Cyclophosphamide; Female; Glomerulonephritis, Membranoproliferative; Hematuria; Humans; Kidney Failure, Chronic; Mycophenolic Acid; Proteinuria; Rituximab; Syndrome; Urticaria; Vasculitis

Subretinal fibrosis and uveitis syndrome is a rare, potentially devastating, posterior uveitis of unknown aetiology, characterised bilaterally by initial multifocal choroiditis with later progressive subretinal fibrosis. We report a rare case of unilateral subretinal fibrosis and uveitis syndrome. To date, there are only two case reports of unilateral disease. Our patient presented with unilateral blur and was found to have reduced visual acuity. A Bartonella profile was positive and a diagnosis of Bartonella posterior uveitis was made. Several positive ocular findings in the anterior chamber and on fundoscopy consistent with the syndrome were found. When steroid therapy alone could no longer control active inflammation, the immunosuppressive agent mycophenolate was added. Over time subretinal fibrosis became established sparing the macula and associated complications occurred, but with mycophenolate, at four years, our patient's visual acuity had improved and remains stable. Moreover, four years after her initial presentation, her condition remains strictly unilateral.

Topics: Adolescent; Bartonella Infections; Female; Fibrosis; Humans; Immunosuppressive Agents; Mycophenolic Acid; Retina; Syndrome; Treatment Outcome; Uveitis; Visual Acuity

While pleuropulmonary involvement in systemic lupus erythematosus (SLE) is a common occurrence, shrinking lung syndrome (SLS) is a rare complication of SLE, particularly in children. We report on a teenager girl with a primary SLE diagnosis, which was based upon clinical, imaging, lung-function and histological findings ascertained to be compatible with SLS. Following a pneumonia, the patient developed inflammatory residues in the lower lobes, an event that probably caused diaphragmatic immobility and subsequently led to SLS. Treatment response to steroids, cyclophosphamide and hydroxychloroquine in this case was excellent, and efficacy was more profound than previously has been reported in the literature with respect to pediatric patients. This case report argues that prognosis of SLS in SLE is likely to be favorable when the diagnosis is made early and the disease is treated appropriately.

Topics: Chest Pain; Child; Cyclophosphamide; Diaphragm; Dyspnea; Female; Humans; Hydroxychloroquine; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Methylprednisolone; Mycophenolic Acid; Pleurisy; Pulmonary Atelectasis; Radiography; Syndrome; Treatment Outcome

Treatment failure occurs in 20% of autoimmune hepatitis patients on prednisolone and azathioprine (AZA). There is no established second line treatment.. To assess the efficacy of mycophenolate mofetil as second line treatment after AZA-intolerance or AZA-nonresponse in autoimmune hepatitis and overlap syndromes.. Consecutive patients from the Dutch Autoimmune Hepatitis Group cohort, consisting of 661 patients, with autoimmune hepatitis or overlap syndromes, AZA-intolerance or AZA-nonresponse and past or present use of mycophenolate mofetil were included. Primary endpoint of mycophenolate mofetil treatment was biochemical remission. Secondary endpoints were biochemical response (without remission), treatment failure and prevention of disease progression.. Forty-five patients treated with mycophenolate mofetil were included. In autoimmune hepatitis remission or response was achieved in 13% and 27% in the AZA-nonresponse group compared to 67% and 0% in the AZA-intolerance group (P = 0.008). In overlap-syndromes remission or response was reached in 57% and 14% in the AZA-nonresponse group and 63% and 25% of the AZA-intolerance group (N.S.); 33% had side effects and 13% discontinued mycophenolate mofetil. Overall 38% had treatment failure; this was 60% in the autoimmune hepatitis AZA-nonresponse group. Decompensated liver cirrhosis, liver transplantations and death were only seen in the autoimmune hepatitis AZA-nonresponse group (P < 0.001).. Mycophenolate mofetil induced response or remission in a majority of patients with autoimmune hepatitis and azathioprine-intolerance and with overlap syndromes, irrespective of intolerance or nonresponse for azathioprine. In autoimmune hepatitis with azathioprine nonresponse mycophenolate mofetil is less often effective.

Topics: Adolescent; Adult; Aged; Child; Cohort Studies; Female; Hepatitis, Autoimmune; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Netherlands; Retrospective Studies; Severity of Illness Index; Syndrome; Treatment Outcome; Young Adult

IIH is a syndrome of increased intracranial pressure characterized by headache, visual disturbance, papilledema with normal cranial neuroimaging. It is associated with many factors in childhood. From the renal perspective renal insufficiency, chronic dialysis, steroid treatment, and recombinant human growth hormone have been associated with IIH. It has also been described in pediatric recipients several months to years following kidney transplantation. In this study, we present a pediatric kidney transplant recipient receiving CyA, prednisone, and mycophenolate mofetil who was discovered to have pseudopapilledema during routine ophthalmological examination. He had no additional signs of increased intracranial pressure. Awareness of possible side effects in the follow-up of these patients may improve management of these children.

Topics: Adolescent; Angiography; Antibodies, Monoclonal; Basiliximab; Cyclosporine; Humans; Kidney Failure, Chronic; Kidney Transplantation; Living Donors; Male; Mycophenolic Acid; Papilledema; Prednisone; Pseudotumor Cerebri; Recombinant Fusion Proteins; Syndrome

Diabetes mellitus and its complications are a public health problem of epidemic proportions. Both diabetes and chronic kidney disease (CKD) increase the risk of acute kidney injury (AKI). Months after a single episode of acute ischaemia to the diabetic kidney, we have found an accelerated progression of nephropathy, with impaired function, severe renal inflammation, microvascular dysfunction, fibrosis and apoptotic cell death. We termed this entity the post-ischaemic inflammatory syndrome. We now test the hypothesis that blocking inflammation ameliorates the post-ischaemic inflammatory syndrome.. Obese-diabetic ZS rats (F(1) hybrids of spontaneously hypertensive heart failure and Zucker fatty diabetic rats) were treated with mycophenolate mofetil (MMF), subjected to renal ischaemia or sham surgery, and monitored via the powerful technique of intravital microscopy.. Amelioration of post-ischaemia inflammation with MMF therapy improved long-term renal function, microvascular dysfunction, fibrosis and apoptosis.. These data support the hypothesis that the post-ischaemic inflammatory syndrome accelerates diabetic CKD, is a critical determinant of injury, and can be successfully treated.

Topics: Animals; Apoptosis; Blood Flow Velocity; Capillary Permeability; Diabetic Nephropathies; Erythrocyte Aggregation; Fibrosis; Immunosuppressive Agents; Intercellular Adhesion Molecule-1; Ischemia; Kidney; Male; Mycophenolic Acid; Nephritis; Rats; Scavenger Receptors, Class E; Syndrome

Topics: Anemia, Hemolytic, Congenital; Child; Female; Humans; Immunosuppressive Agents; Mycophenolic Acid; Purpura, Thrombocytopenic, Idiopathic; Syndrome

Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is characterized by severe systemic autoimmunity caused by mutations in the forkhead box protein 3 (FOXP3) gene. Hematopoietic cell transplantation is currently the only viable option for long-term survival, but patients are frequently very ill and may not tolerate traditional myeloablative conditioning regimens.. Here we present the outcome of hematopoietic cell transplantation using a low-intensity, nonmyeloablative conditioning regimen in 2 patients with IPEX syndrome and significant pretransplant risk factors.. Two high-risk patients with IPEX syndrome received HLA-matched related bone marrow or unrelated peripheral blood stem cell grafts following conditioning with 90 mg/m(2) fludarabine and 4 Gy total body irradiation. Postgrafting immunosuppression consisted of mycophenolate mofetil and cyclosporine. Immune reconstitution and immune function was evaluated by measurement of donor chimerism, regulatory T-cell numbers, absolute lymphocyte subsets, and T-cell proliferation assays.. Both patients experienced minimal conditioning toxicity and successfully engrafted after hematopoietic cell transplantation. With a follow-up of 4 and 1 years, respectively, patients 1 and 2 have full immune function and normal FOXP3 protein expression.. A low-intensity, nonmyeloablative conditioning regimen can establish stable engraftment and correct the life-threatening immune deficiency and enteropathy of IPEX syndrome despite the presence of comorbidities that preclude conventional hematopoietic cell transplantation.

Topics: Adolescent; Cell Separation; Child; Cyclosporine; Flow Cytometry; Forkhead Transcription Factors; Genetic Diseases, X-Linked; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunologic Deficiency Syndromes; Immunosuppressive Agents; Infant; Male; Mycophenolic Acid; Myeloablative Agonists; Reverse Transcriptase Polymerase Chain Reaction; Syndrome; Transplantation Conditioning; Vidarabine; Whole-Body Irradiation

The authors report on a 55-year-old female patient after R1 resection of a malignant thymoma with spindle type epithelial cells (WHO type A, Masaoka stage III) referred for further therapy of an ulcerative colitis. At that time, both adjuvant radiation and cytostatic therapy were not applicable due to severe activity of the ulcerative colitis. Under immunosuppressive treatment with azathioprine and steroids, the patient developed cytomegalovirus (CMV) enteritis which was triggered by therapy-induced leukopenia. After a switch from azathioprine to mycophenolatmofetil (MMF) treatment and administration of cidofovir because of nonresponse to ganciclovir and incompatibility of foscarnet sodium (Foscavir), the patient clinically improved. In addition, the patient was treated with immunoglobulins every 3-4 weeks because of antibody deficiency. At present, 3.5 years after R1 resection, the patient still has no clues of a remaining tumor mass under current immunosuppressive therapy. Ulcerative colitis is also in complete remission stage.. This case indicates the very rare features of a syndrome with thymoma and antibody deficiency which was first described by Robert Good. Furthermore, the impact of immunosuppressive therapy and management of opportunistic infections on the course of this disease is obvious.

Topics: Agammaglobulinemia; Antiviral Agents; Azathioprine; Cidofovir; Colitis, Ulcerative; Cytomegalovirus Infections; Cytosine; Enteritis; Female; Humans; Immunization, Passive; Immunologic Deficiency Syndromes; Immunosuppressive Agents; Leukopenia; Middle Aged; Mycophenolic Acid; Neoplasm Staging; Opportunistic Infections; Organophosphonates; Postoperative Complications; Syndrome; Thymectomy; Thymoma; Thymus Neoplasms

A scleroderma-like cutaneous syndrome, occurring after implantation of a prosthetic knee joint in an elderly woman, is reported. This case did not seem to typically fit into any of the known scleroderma-like disorders of the skin described to date. The patient was shown to be sensitized to metals contained in the prosthesis and to mount a Th2-type immune response concomitantly with development of skin fibrosis. In particular, eosinophilia, markedly elevated serum IgE levels, in vitro spontaneous production of interleukin (IL)-4 by T lymphocytes, and elevated serum levels of Th2 cytokines (namely, IL-4, IL-5, and IL-13) were observed during the acute phase of illness. Since eosinophils and such Th2 cytokines as IL-13 also have recognized fibrogenic properties, it is speculated that the pathogenesis of skin fibrosis in this case could have been the direct and/or indirect consequence of the coexisting Th2-type immune response.

Topics: Aged; Arthroplasty, Replacement, Knee; Cobalt; Cytokines; Eosinophilia; Erythema; Female; Humans; Immunoglobulin E; Immunosuppressive Agents; Knee Prosthesis; Mycophenolic Acid; Pregnenediones; Scleroderma, Limited; Syndrome

A newborn female infant born to a woman on immunosuppressive medications including mycophenolate mofetil (MMF) for a renal graft secondary to lupus nephritis presented with congenital diaphragmatic hernia (CDH) and additional findings of microtia, esophageal atresia with tracheoesophageal fistula, cleft palate, congenital heart defect, digital anomalies, and dysmorphic facial features. Pulmonary hypoplasia resulted in death at day 2 of life. She was presumed to have Fryns syndrome based on diagnostic criteria established for this recessive disorder with prominent features including CDH, facial anomalies, and nail hypoplasia. In retrospect, this infant's findings are more likely the result of teratogenic exposure to MMF, as more recent data have emerged linking aural atresia, digital anomalies, and dysmorphic features to this drug. To date, this is the only human report of CDH in an infant with prenatal exposure to MMF, although the manufacturer's package insert alludes to animal studies with a broad spectrum of malformations, including CDH. Thus, a teratogenic exposure can mimic a known Mendelian genetic syndrome, and caution is urged in presuming a genetic etiology for infants with potential teratogenic exposure to relatively new drugs with limited published animal data.

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Autopsy; Ear; Fatal Outcome; Female; Hernia, Diaphragmatic; Hernias, Diaphragmatic, Congenital; Humans; Immunosuppressive Agents; Infant, Newborn; Mycophenolic Acid; Pregnancy; Radiography; Syndrome; Teratogens

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

Pulmonary-renal syndrome (PRS) associated with antineutrophil cytoplasmic antibodies (ANCA)-negative microscopic polyangiitis (MPA) is relatively rare, and the effects of plasmapheresis on these patients remain unclear. Here, we report the case of a 66-year-old man who presented with fever, acute renal failure, thrombocytopenia, and sudden onset of diffuse pulmonary hemorrhage. Prompt plasmapheresis and concurrent pulse therapy with methylprednisolone effectively rescued his pulmonary-renal syndrome. The patient was then diagnosed with MPA on the basis of typical histological findings and the absence of surrogate markers of Wegener's granulomatosis and Churg-Strauss syndrome. This case demonstrates the therapeutic effects of plasmapheresis on ANCA-negative MPA and highlights the necessity of prompt plasmapheresis for not only resolving pulmonary hemorrhage but also increasing the likelihood of renal function restoration in patients with PRS.

Topics: Administration, Oral; Aged; Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Antineutrophil Cytoplasmic; Glucocorticoids; Humans; Kidney Diseases; Lung Diseases; Male; Microscopic Polyangiitis; Mycophenolic Acid; Plasmapheresis; Prednisolone; Pulse Therapy, Drug; Radiography, Thoracic; Syndrome; Treatment Outcome

Topics: Abnormalities, Multiple; Female; Humans; Infant, Newborn; Mycophenolic Acid; Syndrome

Topics: Adolescent; Anti-Inflammatory Agents, Non-Steroidal; Humans; Male; Mycophenolic Acid; Nephritis, Interstitial; Syndrome; Uveitis

Topics: Acute Disease; Adult; Female; Humans; Immunosuppressive Agents; Inflammation; Lupus Erythematosus, Systemic; Mycophenolic Acid; Syndrome

Topics: Adult; Arthritis; Autoantibodies; Female; Histidine-tRNA Ligase; Humans; Immunosuppressive Agents; Mycophenolic Acid; Polymyositis; Raynaud Disease; Remission Induction; Syndrome

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

Autoimmune lymphoproliferative syndrome (ALPS) is a disorder due to a genetic defect concerning programmed cell death (apoptosis). Most patients are carriers of a heterozygous mutation affecting the TNFRSF6 (Fas). Treatment of autoimmune complications of ALPS includes corticosteroids, gamma-globulin infusions, and in refractory cases, splenectomy, cytostatic agents, and bone marrow transplantation. A 10-year-old boy with ALPS manifested by recurrent febrile episodes, lymphadenopathy, splenomegaly, and cytopenias refractory to corticosteroid therapy is presented. Treatment with mycophenolate mofetil, an immunosuppressive agent typically used in organ transplantation was initiated. This treatment was successful with resolution of thrombocytopenia, decrease in lymphadenopathy, and improvement of his general clinical condition for over 2 years of duration.

Topics: Adrenal Cortex Hormones; Autoimmune Diseases; Child; fas Receptor; Humans; Immunosuppressive Agents; Lymphoproliferative Disorders; Male; Mutation; Mycophenolic Acid; Syndrome; Thrombocytopenia; Time Factors

Topics: Adult; Cyclophosphamide; Diagnosis, Differential; Diagnostic Errors; Drug Therapy, Combination; Female; Fluorescein Angiography; Fundus Oculi; Glucocorticoids; Hearing Loss, Sensorineural; Humans; Methylprednisolone Hemisuccinate; Mycophenolic Acid; Nervous System Diseases; Prednisone; Retinal Artery Occlusion; Syndrome

TINU syndrome probably is a frequently overlooked disease where uveitis occurs in association with acute tubulointerstitial nephritis. Diagnostic criteria have been published recently.. In this retrospective case series the charts of four consecutive patients with TINU syndrome (follow-up 36, 23, 17, and 12 months, respectively) were analysed, including comorbidity and complications, and the literature was reviewed.. Two patients were treated with methotrexate or ciclosporin A and mycophenolate mofetil. In one patient autoimmune thyroiditis was known. During the follow-up, symptoms indicative of rheumatoid arthritis were observed. Because of her uveitis she required methotrexate therapy. Three patients were obese (mean BMI 32.2 kg/m (2)). Ocular complications were posterior synechiae (two patients) and papillary and macular oedema (three patients). One patient developed cerebrospinal hypertension under ciclosporin A treatment which resolved after discontinuation of therapy.. Patients with definite TINU syndrome frequently suffer from other diseases and associated immune phenomena. The course of the disease can vary considerably. Complications do occur, despite overall good prognosis. Regional and systemic steroids may be sufficient; frequently steroid sparing immunosuppressives are necessary at least temporarily. Patients with this multiorgan disease do need to be followed by a paediatrician or a medical specialist.

Topics: Adolescent; Arthritis, Rheumatoid; Autoimmune Diseases; Child; Cyclosporine; Female; Follow-Up Studies; Humans; Male; Methotrexate; Mycophenolic Acid; Nephritis, Interstitial; Patient Care Team; Syndrome; Thyroiditis, Autoimmune; Treatment Outcome; Uveitis

Mycophenolate mofetil 1.5 g daily (30 mg/kg body weight) was given to a patient with ankylosing spondylitis, ulcerative colitis, and severe refractory polymyositis after conventional treatment regimes had failed. No severe side effects occurred. Considerable improvement of clinical symptoms and electromyographic findings were seen within 6 months after the initiation of mycophenolate mofetil, allowing for tapering and discontinuation of methylprednisolone. Mycophenolate mofetil may be considered as an useful alternative in the treatment of polymyositis when standard therapeutic regimens fail.

Topics: Anti-Inflammatory Agents; Autoimmune Diseases; Colitis, Ulcerative; Electromyography; Female; Humans; Immunosuppressive Agents; Methylprednisolone; Middle Aged; Mycophenolic Acid; Pleurisy; Polymyositis; Retreatment; Spondylitis, Ankylosing; Syndrome

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: Adult; Female; Hepatitis C; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Myasthenia Gravis; Mycophenolic Acid; Syndrome