mycophenolic-acid and Antiphospholipid-Syndrome

Systemic lupus erythematosus is an autoimmune connective-tissue disorder with a wide range of clinical features, which predominantly affects women, especially from certain ethnic groups. Diagnosis is based on clinical assessment supported by investigations, including the finding of autoantibodies. Treatments range from antimalarial agents to corticosteroids and immunosuppressive agents. This Seminar draws attention to advances in the epidemiology, genetics, cardiovascular risks, lupus nephritis, CNS disease, the antiphospholipid syndrome, assessment of disease activity and damage, and pregnancy related and quality of life issues. New therapeutic approaches, such as biological agents and mycophenolate mofetil, will also be discussed.

Topics: Adult; Antiphospholipid Syndrome; Cyclophosphamide; Female; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Lupus Nephritis; Male; Mycophenolic Acid; Prevalence

This study describes the pharmacokinetics of mycophenolate mofetil (MMF) in 15 pediatric patients with vasculitis and connective tissue disease involving the kidney. Patients included 10 with systemic lupus erythematosus (SLE), 1 with antiphospholipid antibody syndrome, 2 with Wegener granulomatosis, and 1 each with Goodpasture syndrome, Henoch-Schönlein-associated nephritis, and 1 with severe tubulointerstitial nephritis and uveitis. All patients were treated with steroids and additional therapy prior to treatment with MMF, which was administered for a median of 491 days. Mean starting dose of MMF was 974+/-282 mg/m(2 )in two divided doses. Pharmacokinetic monitoring of the active compound of MMF, mycophenolic acid (MPA), was performed using an EMIT assay. The mean MPA AUC after a median of 39 days was 61.8+/-31.0 micro gxh/ml, median time to maximum concentration was 60 min, and mean maximum concentration was 18.5+/-8.4 micro g/ml. At last follow-up, mean MMF dose was 900+/-341 mg/m(2) per day, and mean trough MPA concentration was 3.1+/-1.1 (range 0.6-4.6) micro g/ml. Therapy was effective in inducing remission in 4 of 9 patients with active disease. Only 1 of the 5 other patients relapsed. All 6 patients with controlled disease maintained remission. There were few side effects: one episode each of diarrhea and leukocytopenia and two viral infections. We conclude that MMF at 900 mg/m(2) per day appears to be effective in these patients.

Topics: Adolescent; Anti-Glomerular Basement Membrane Disease; Antiphospholipid Syndrome; Autoimmune Diseases; Child; Female; Granulomatosis with Polyangiitis; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Male; Mycophenolic Acid; Nephritis, Interstitial; Remission Induction; Treatment Outcome

The risk of life-threatening complications, such as visceral disseminated varicella zoster virus (VZV) infection, is greater in immunosuppressed individuals, such as systemic lupus erythematosus (SLE) patients.. Here, a case is reported of a Caucasian woman diagnosed with lupus nephritis and anti-phospholipid syndrome, who was subjected to mycophenolate mofetil and high-dose steroid remission-induction therapy. Two months later she developed abdominal pain followed by a fatal rapid multi-organ failure. As no typical skin rashes were evident, death was initially attributed to catastrophic anti-phospholipid syndrome. However, autopsy and virological examinations on archival material revealed a disseminated VZV infection.. Overall, this case highlights the importance of having a high clinical suspicion of fatal VZV infections in heavily immunosuppressed SLE patients even when typical signs and symptoms are lacking.

Topics: Abdominal Pain; Antiphospholipid Syndrome; Fatal Outcome; Female; Herpes Zoster; Herpesvirus 3, Human; Humans; Immunocompromised Host; Lupus Nephritis; Middle Aged; Mycophenolic Acid; Real-Time Polymerase Chain Reaction; Steroids

A 52-year-old man presented to our cardiology service for an elective diagnostic coronary angiogram for risk stratification in the context of stable angina. He was diagnosed with antiphospholipid syndrome 2 years prior and had three known thrombotic episodes in the form of a stroke, retinal artery occlusion and deep vein thrombosis. Our initial differential was atherosclerotic coronary artery disease, however, coronary angiography demonstrated a dominant right coronary artery with a long segment of chronic spontaneous dissection distally but with thrombolysis in myocardial infarction III flow. He was treated medically with antianginals which rendered him asymptomatic and is currently on regular follow-up in the cardiology outpatient department.

Topics: Angina, Stable; Angiography; Antibiotics, Antineoplastic; Anticoagulants; Antiphospholipid Syndrome; Calcium Channel Blockers; Coronary Vessel Anomalies; Diagnosis, Differential; Humans; Male; Middle Aged; Mycophenolic Acid; Myocardial Infarction; Treatment Outcome; Vascular Diseases

We discuss two patients with antiphospholipid syndrome (APS) who presented with critical ischemia of both lower extremities due to arterial microthrombi. They received multimodality therapy emergently: anticoagulation, immunosuppression, and therapeutic plasma exchange (TPE). Then they were maintained on anticoagulation with fondaparinux and immunosuppression with mycophenolate mofetil (MMF), and were followed for 4 years.. Two patients with APS with ischemia and necrosis of their distal lower extremities were treated emergently with anticoagulation (intravenous heparin), immunosuppression (prednisone), and TPE. They were maintained on anticoagulation with fondaparinux and immunosuppression with MMF.. Neither patient had recurrent microthrombotic disease during a 4-year follow-up.. As described in our small cohort, patients with APS who suffer from microthrombotic arterial disease may benefit from maintenance therapy of anticoagulation with fondaparinux and immunosuppression with MMF, an approach which may be worthy of further trial. Fondaparinux does not require attention to diet, monitoring, and cumbersome bridging that is typical of warfarin therapy. MMF provides immunosuppression while sparing the side effects of steroid treatment.

Topics: Adult; Anticoagulants; Antiphospholipid Syndrome; Combined Modality Therapy; Female; Follow-Up Studies; Fondaparinux; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Plasma Exchange; Thrombosis; Treatment Outcome

Topics: Adult; Anticoagulants; Antiphospholipid Syndrome; Biopsy; Glucocorticoids; Hepatic Infarction; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Liver; Lupus Erythematosus, Systemic; Magnetic Resonance Imaging; Male; Mycophenolic Acid; Tomography, X-Ray Computed; Treatment Outcome

Mycophenolate mofetil (MMF) is an effective therapeutic agent with high safety profile in the management of lupus nephritis. This retrospective study was conducted to assess the efficacy and side effect profile of MMF as induction as well as maintenance therapeutic agent along with tapering steroids in neuropsychiatric lupus (NPSLE). Hospital electronic medical records of patients with SLE diagnosed by ACR 1990 and/or SLICC 2012 criteria between January 2005 and May 2015 were retrieved. Among them, patients fulfilling ACR 1999 criteria for NPSLE were identified. Data of NPSLE patients treated with MMF as upfront second line immunosuppressive agent, both for induction and maintenance, were analyzed. Of the 140 patients with NPSLE, 88 fulfilled the inclusion criteria. Mean age of the cohort was 25.51 ± 7.82 years with female to male ratio of 84:4. Median duration of follow-up was 33 months (3-129 months). Seizure was the most common NPSLE manifestation (n = 37, 42.05%). Of the 88 patients, 18 had NPSLE solely due to secondary antiphospholipid syndrome. Of the remaining 70 patients, 61 (87.1%) had improved, 7 remained unchanged with no worsening and 3 patients had worsening or developed new symptoms during follow up after 3 months from baseline. At last follow-up, 55 out of 57 patients (97.1%) with detailed data had improved, while 2 patients had relapsed. Side effects were significantly more common in patients on prednisolone as compared to those on deflazacort. In patients with NPSLE, MMF along with tapering steroids is an efficacious combo in inducing remission and preventing relapse of disease.

Topics: Adolescent; Adult; Age Factors; Antiphospholipid Syndrome; Brain; Electronic Health Records; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; India; Lupus Nephritis; Male; Mycophenolic Acid; Prednisolone; Pregnenediones; Recurrence; Remission Induction; Retrospective Studies; Seizures; Steroids; Tertiary Care Centers; Young Adult

Topics: Adolescent; Anti-Inflammatory Agents, Non-Steroidal; Antiphospholipid Syndrome; Aspirin; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Male; Methylprednisolone; Movement Disorders; Mycophenolic Acid; Prednisolone

Two patients with systemic lupus erythematosus presented with vision loss, and were diagnosed with retinal vasculopathy. Patient 1 had occlusive vasculitis with macular oedema and retinal ischaemia in the right eye. Corticosteroid therapy was increased and intravenous rituximab added. Intravitreal therapy and panretinal photocoagulation were performed. Patient 2 presented with a left central retinal vein occlusion without vasculitis but was on anticoagulation therapy due to having an antiphospholipid syndrome. Both patients maintained a stable visual acuity.. Occlusive lupus retinal vasculitis has severe visual and systemic consequences (central nervous system vasculitis). It is crucial to differentiate it from standard vascular occlusion syndromes.

Topics: Acenocoumarol; Antibodies, Monoclonal, Murine-Derived; Anticoagulants; Antiphospholipid Syndrome; Cataract; Diagnosis, Differential; Female; Fluorescein Angiography; Humans; Immunosuppressive Agents; Ischemia; Lupus Erythematosus, Systemic; Macular Edema; Middle Aged; Mycophenolic Acid; Prednisone; Retinal Vasculitis; Retinal Vein Occlusion; Rituximab; Tomography, Optical Coherence

The skin is one of the target organs most commonly affected in lupus erythematosus (LE) and a wide range of cutaneous changes have been described in LE patients. Papulonodular mucinosis (PNM) in particular is an uncommon cutaneous manifestation of LE. We discuss the case of a 26-year-old Senegalese woman with systemic LE and antiphospholipid syndrome (APS) who presented with pruritic papules on her back and extremities that appeared when she was on vacation in Africa and non-compliant with medications. Histopathologic examination was consistent with PNM. The patient was treated with mycophenolate mofetil and hydroxychloroquine, with subjective relief in pruritis at 6-week follow-up. To our knowledge, this is the first case of PNM presenting in a patient with both SLE and APS. Whether APS contributes to the pathogenesis of PNM is currently unknown.

Topics: Adult; Antiphospholipid Syndrome; Female; Follow-Up Studies; Humans; Hydroxychloroquine; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Mucinoses; Mycophenolic Acid

Topics: Acyclovir; Antiphospholipid Syndrome; Antiviral Agents; Drug Therapy, Combination; Female; Herpes Zoster; Humans; Immunosuppressive Agents; Infusions, Intravenous; Lupus Erythematosus, Systemic; Middle Aged; Mycophenolic Acid; Necrosis; Prednisone; Skin

Unresponsive autoimmune haemolytic anaemia (AIHA) may require therapy with second-line drugs. There is no consensus that any one of these agents is more effective than another. Mycophenolate mofetil (MMF) is an immunosuppressive drug proven to be effective in reducing renal allograft rejection as well as being used in autoimmune diseases including systemic lupus erythematosus (SLE). We describe its use in two patients who were treated with MMF for AIHA in the context of underlying SLE and antiphospholipid syndrome (APS). The patients showed a good response to treatment with MMF, suggesting a possible role in the treatment of AIHA.

Topics: Adult; Anemia, Hemolytic, Autoimmune; Antiphospholipid Syndrome; Antirheumatic Agents; Female; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Middle Aged; Mycophenolic Acid

Topics: Adjuvants, Immunologic; Age Factors; Antimalarials; Antiphospholipid Syndrome; Cyclophosphamide; Dehydroepiandrosterone; Female; Heart Diseases; Humans; Immunosuppressive Agents; Kidney Diseases; Lupus Erythematosus, Systemic; Male; Middle Aged; Mycophenolic Acid; Neoplasms