mycophenolic-acid and Pancytopenia

Anemia, leukopenia, and/or thrombocytopenia can occur as a result of non-immune- and immune-mediated mechanisms in patients with systemic lupus erythematosus. Although the differential diagnosis of these cytopenias is broad and warrants a thorough evaluation, lupus disease activity and medications are common etiologic factors. Corticosteroids are the mainstay of initial treatment for immune-mediated hemolytic anemia and severe thrombocytopenia; immunosuppressive agents such as mycophenolate mofetil or azathioprine are often added for their steroid-sparing effects. Rituximab and intravenous immunoglobulin can be considered for refractory cytopenias based on a large body of anecdotal evidence and case series. Newer biologic agents such as belimumab or epratuzumab have yet to be studied specifically in systemic lupus erythematosus-mediated hematologic disorders.

Topics: Anemia; Antibodies, Monoclonal, Murine-Derived; Azathioprine; Glucocorticoids; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Leukopenia; Lupus Erythematosus, Systemic; Mycophenolic Acid; Pancytopenia; Rituximab; Thrombocytopenia

Systemic lupus erythematosus is a multi-organ inflammatory autoimmune disease; immune complexes are part of the pathogenesis, but not entirely responsible. Trisomy X is the most common female chromosomal abnormality and the role of an additional X chromosome in the development of systemic lupus erythematosus is well recognized. However, the potential complications and optimal management of childhood lupus with trisomy X remain unclear. Herein, we describe a case of childhood-onset systemic lupus erythematosus associated with severe bone complications presumably secondary to trisomy X.. A 16-year-old Japanese girl was diagnosed with childhood-onset systemic lupus erythematosus and trisomy X. A chromosomal abnormality (47, XXX) was incidentally identified on bone marrow examination initially done to determine the cause of pancytopenia. She had a persistent headache, fever　for six days, diffuse hair loss, mucosal ulcers, butterfly eruptions, and palmar erythema. Furthermore, thrombocytopenia, anemia, and erythrocyte fragmentation were detected, suggesting secondary thrombotic microangiopathy. She was initially treated with intravenous methylprednisolone pulse therapy and prescribed monthly cyclophosphamide for severe disease activity, prednisolone, mycophenolate mofetil, and hydroxychloroquine as remission maintenance drugs. She developed generalized extremity pain that had been worsening throughout the disease. Extremity magnetic resonance imaging performed 12 months after the treatment onset revealed multifocal avascular necrosis, and dual-energy X-ray absorptiometry revealed further decreased bone mineral density. High plasma levels of factor VIII were detected by additional tests for coagulation functions, and we suspected the possibility that factor VIII might cause avascular necrosis due to thrombosis. Currently, she is being treated with prednisolone and MMF for SLE. However, her extremity pain has not been managed effectively even under the administration of non-steroidal anti-inflammatory drugs and pregabalin.. An additional X chromosome has been reported to be associated with factor VIII and osteoporosis. Additionally, elevated plasma levels of FVIII is the risk factors for thrombosis, which leads to the risk of avascular necrosis. Patients with systemic lupus erythematosus complicated by trisomy X might be at a higher risk of avascular necrosis and osteoporosis that can also manifest in childhood systemic lupus erythematosus.

Topics: Adolescent; Antirheumatic Agents; Bone Marrow Examination; Chromosomes, Human, X; Cyclophosphamide; Factor VIII; Female; Humans; Lupus Erythematosus, Systemic; Medication Therapy Management; Methylprednisolone; Mycophenolic Acid; Osteonecrosis; Osteoporosis; Pancytopenia; Severity of Illness Index; Sex Chromosome Aberrations; Sex Chromosome Disorders of Sex Development; Thrombosis; Trisomy

Autoimmune diseases are sometimes associated with immune-mediated renal diseases and cryoglobulinemia is one of the causes. Cryoglobulinemia and cryoglobulinemic glomerulonephritis associated with primary Sjögren's syndrome are most frequent condition among non-hepatitis C virus-related condition. Its typical renal manifestation shows high amount of proteinuria with microscopic hematuria and renal insufficiency. We describe a case of 72-year-old woman with Hashimoto disease, autoimmune hepatitis, Sjögren's syndrome, and immune-related pancytopenia complicated by cryoglobulinemic glomerulonephritis. Before kidney biopsy, tubulointerstitial nephritis probably due to Sjögren's syndrome was suspected because of persistent hematuria without significant proteinuria and developing mild renal dysfunction over 6 months. The developing renal dysfunction associated with isolated hematuria is uncommon in glomerular diseases. Kidney biopsy, however, revealed established membranoproliferative glomerulonephritis with subendothelial deposits consisting of tubular structures with IgM, IgG, and C3 staining. Corticosteroids plus mycophenolate mofetil therapy successfully normalized renal function. Physician should not overlook cryoglobulinemic glomerulonephritis, which is potentially poor prognosis, even if urinalysis shows only persistent isolated hematuria in patients with autoimmune diseases.

Topics: Adrenal Cortex Hormones; Aged; Antibiotics, Antineoplastic; Autoimmune Diseases; Cryoglobulinemia; Female; Glomerulonephritis; Glomerulonephritis, Membranoproliferative; Hashimoto Disease; Hematuria; Hepatitis, Autoimmune; Humans; Kidney; Methylprednisolone; Mycophenolic Acid; Nephritis, Interstitial; Pancytopenia; Renal Insufficiency; Sjogren's Syndrome; Treatment Outcome

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

Topics: Humans; Immunoglobulins, Intravenous; Lupus Erythematosus, Systemic; Mycophenolic Acid; Pancytopenia; Primary Myelofibrosis

Hematological abnormalities, such as anemia, leucopenia, and thrombocytopenia, secondary to peripheral destruction, are common in systemic lupus erythematosus (SLE). However, cytopenias from autoimmune myelofibrosis (AIMF) are extremely uncommon in SLE, with less than 40 reported cases in the literature. We report the case of a 33-year-old female who presented with bullous skin lesions and pancytopenia as the presenting manifestation of what was ultimately diagnosed as SLE with AIMF. She responded well to glucocorticoids and mycophenolate mofetil.

Topics: Adult; Autoimmune Diseases; Biopsy; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Mycophenolic Acid; Pancytopenia; Prednisone; Primary Myelofibrosis; Treatment Outcome

Autoimmune hepatitis (AIH) is an immune-mediated chronic liver disease characterized by hepatocellular inflammation, necrosis, and fibrosis, which can progress to cirrhosis and fulminant hepatic failure. The standard treatment for AIH includes corticosteroids alone or in combination with azathioprine. Although most patients achieve remission using the standard regimen, some patients do not respond due to either drug intolerance or refractory disease; in such cases alternative immunosuppressive agents should be explored. The second-line therapies are cyclophilin inhibitors such as cyclosporine A or tacrolimus, and nowadays mycophenolate mofetil (MMF) is widely used if azathioprine-based therapies are not tolerated. Although these are recommended as an alternative to the first-line regimen, there is insufficient evidence for the efficacy of second-line therapies, with the evidence based mainly on expert opinion. Therefore, we report an AIH patient receiving the standard regimen in whom remission did not occur due to side effects to azathioprine, but was successfully treated with MMF in combination with corticosteroids as an alternative to the standard regimen.

Topics: Alanine Transaminase; Alopecia; Antibiotics, Antineoplastic; Aspartate Aminotransferases; Azathioprine; Female; Hepatitis, Autoimmune; Humans; Liver; Middle Aged; Mycophenolic Acid; Pancytopenia; Prednisolone

Mycophenolate mofetil (MMF) decreases the risk of acute rejection and is associated with improved graft survival in renal transplant recipients. However, MMF-related side effects often necessitate dose reduction, which may expose patients to a higher risk of acute rejection and graft loss. This study's aim was to examine the reasons for MMF dose reduction during the first post-transplant year and its impact on acute rejection, overall and death-censored graft loss.. Single-center retrospective analysis of 749 renal transplant recipients treated with MMF in their initial maintenance immunosuppressive protocol.. In 365 patients (48.7%) a total of 530 MMF dose reductions were done. Reasons for reduction were hematologic toxicity (46.5%), infection (16.1%), gastrointestinal side effects (12.3%), malignancy (2.1%), study protocol (14.6%), and unknown (13.5%). MMF dose reduction as such was not an independent predictor of acute rejection or graft survival, although reductions in ≥ 50% of initial dose were significantly associated with acute rejection.. In this retrospective cohort, by far the most important reason for MMF dose reduction during the first post-transplantation year was hematologic. MMF dose reductions in ≥ 50% increased the risk of acute rejection but did not compromise graft survival.

Topics: Adult; Aged; Anemia; Female; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Kidney Transplantation; Leukopenia; Male; Middle Aged; Mycophenolic Acid; Pancytopenia; Retrospective Studies; Thrombocytopenia

Topics: Acute Kidney Injury; Adult; Blood Component Transfusion; Bone Marrow; Cell Lineage; Combined Modality Therapy; Darbepoetin alfa; Erythropoietin; Filgrastim; Granulocyte Colony-Stimulating Factor; Hematuria; Humans; Lupus Erythematosus, Systemic; Lupus Nephritis; Lymphohistiocytosis, Hemophagocytic; Male; Mycophenolic Acid; Myelodysplastic Syndromes; Pancytopenia; Pericarditis; Prednisone; Proteinuria; Recombinant Proteins

An increase in leucocyte apoptosis and impaired clearance of apoptotic cells has been observed in patients with systemic lupus erythematosus (SLE). Apoptotic cells are likely to be a key source of autoantigens in SLE as they express many of the nuclear autoantigens (in surface blebs and apoptotic bodies) that are relevant to this disease. The clearance of apoptotic cells is usually a rapid process, such that few cells are usually seen in the extracellular environment in vivo. We report a case in which multiple apoptotic bodies were observed in the bone marrow of a patient with SLE that was complicated by an immune-mediated pancytopenia. We have subsequently examined the frequency of apoptotic cells, identified morphologically, and by caspase-3 staining in bone-marrow trephine samples taken from patients with SLE over a 10-year period of follow-up. A high proportion of bone marrows contained apoptotic debris. The novel demonstration of apoptotic bodies in vivo in patients with SLE is unusual and supports the notion that the marrow may be a target organ in the disease. Their abundance is also consistent with the hypothesis that normal clearance mechanisms are defective and/or overwhelmed in SLE.

Topics: Adult; Apoptosis; Autoimmunity; Bone Marrow; Caspase 3; Female; Granulocyte Colony-Stimulating Factor; Humans; Immunologic Factors; Immunosuppressive Agents; Leukocytes; Lupus Erythematosus, Systemic; Male; Methylprednisolone; Middle Aged; Mycophenolic Acid; Pancytopenia; Staining and Labeling