Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Background: Premature ovarian failure (POF) is often associated with autoimmune disorders. The 47,XXX karyotype has also been associated with POF and other genitourinary abnormalities. Following is a case of a 17 year old with immune thrombocytopenic purpura (ITP), POF, 47, XXX and a positive antinuclear antibody (ANA).Case Report: A 17 year old Caucasian female was referred to the Adolescent Health Clinic for evaluation of oligomenorrhea with secondary amenorrhea. Thelarche occurred at 12 years, and menarche at 13 years of age. Since then she had a total of five menstrual periods, spaced 1-15 months apart and lasting 3-5 days. Her last menstrual period was six months prior to presentation. Past medical history was significant for chronic ITP diagnosed seven months prior to presentation, when she developed easy bruising. She was treated with IV gamma globulin and had a moderate response, but relapsed several weeks later. She was started on oral prednisone and had a good response, but continued to relapse whenever steroids were tapered. She was therefore maintained on prednisone 10 mg QOD. There was no family history of irregular menses or autoimmune disease. Physical exam revealed a well-appearing, slightly Cushingoid 17 year old. Physical and cognitive development were age-appropriate. There were no stigmata of Turner Syndrome. The thyroid was normal. Breasts were Tanner 5; public hair was Tanner 3. The external genitalia were normal and appeared well-estrogenized. The remainder of the exam was unremarkable. Pelvic ultrasound demonstrated a normal uterus and ovaries. Laboratory evaluation was significant for elevated gonadotropins and nondetectable estradiol. ANA was positive at 1:320 with a speckled pattern. Blood counts, serologies, complement levels, and coagulation studies were otherwise normal. Cytogenetic studies revealed a 47,XXX karyotype. The patient was placed on an estrogen/norethindrone hormone replacement patch for premature ovarian failure. To date, she has developed no further symptoms, and does not meet criteria for a diagnosis of systemic lupus erythematosis.Conclusions: A 47,XXX karyotype was found in a 17 year old with POF and ITP with a positive ANA. The presence of known autoimmune disease in a woman with POF should not dissuade the physician from evaluating for a potential genetic cause.
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PMID:47,Xxx in an adolescent with premature ovarian failure and autoimmune disease 1086 83

Twenty-nine patients with systemic lupus erythematosus were treated with a new synthetic unsaturated prednisolone derivative, triamcinolone, for as long as 11 months. This hormone is 1.3 times as powerful as prednisone and 4.4 times more potent than hydrocortisone as an anti-inflammatory agent. The average dose for beginning therapy in cases of mild systemic lupus erythematosus was 20.6 mg. a day. The average maintenance dose used to control mild exacerbations of the disease was 26.0 mg. a day. There was no evidence of sodium retention or potassium loss. Sixteen patients had upper gastrointestinal x-ray studies before and during therapy with triamcinolone. There was no evidence of peptic ulceration except in one patient who was receiving 96 mg. a day. Nine patients had gastric analysis with histamine before and during therapy. No significant changes were noted in results of these tests, even in the patient who had an ulcer. No abnormal increase in uropepsin was noted in cases in which this factor was tested. The pattern of clinical improvement closely paralleled that obtained by previous treatment with older steroids. There was a disappearance of all the clinical and laboratory abnormalities produced by the disease, with the exception of long standing renal involvement. A major difference between triamcinolone and other steroids was a tendency to progressive gradual loss of weight, partly owing to fluid loss. Cushingoid appearance produced by other steroid therapy did not disappear. The cutaneous side effects, particularly Cushingoid appearance, hirsutism and striae were more pronounced than with older steroids. The most serious side effect was muscle weakness which appeared in six patients, all women, in from four to thirty-two weeks after starting triamcinolone. The profound muscle weakness, most pronounced in the quadriceps group, gradually cleared after several weeks of therapy with another steroid. Fourteen patients had received prior steroid therapy with all the older anti-inflammatory hormones and seven of them were better controlled and felt better with triamcinolone.
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PMID:Systemic lupus erythematosus; results of treatment with triamcinolone. 1357 87

We report on the unique effects and benefits of autologous stem cell transplantation in childhood systemic lupus erythematosus (SLE) and describe this procedure in two young girls with severe and refractory disease. The patients' stem cells were mobilized with granulocyte colony-stimulating factor (G-CSF) and collected by CS-3000 Blood Cell Separator (Baxter Healthcare, Round Lake, Ill., USA), and the CliniMACS CD34+ cell selection device (Miltenyi Biotech, Bergisch Gladbach, Germany) was used to obtain CD34+ cells. A total of 1.7x10(6) and 1.0x10(6)/kg CD34+ cells were obtained, with 2.0x10(5) and 1.0x10(4)/kg of CD3+ cells remaining, respectively. The conditioning regimen consisted of cyclophosphamide (50 mg/kg per day for 4 days) plus antithymocyte globulin (ATG-Fresenius, 5 mg/kg per day for 3 days). Neutrophil counts recovered within 9 days in both cases. Within 15 days, the platelet counts recovered and were sustained over 100x10(9)/l. Cushingoid features disappeared completely 3 months after transplantation because of the removal of corticosteroid medication. One 13-year-old child increased her height by 5 cm in 6 months after stopping steroids. She had not increased her height in her previous 7 years of disease. As of the time of this report, the first patient remains in clinical and laboratory remission for nearly 4 years, while the second suffered a relapse of thrombocytopenia 9 months post-transplantation. One residual effect of their treatment is that their CD4+ cell counts remained in the lower range after one year of transplant. The effect of this conditioning regimen plus CD34+ autologous stem cell transplantation on these two children with refractory SLE was beneficial, but long-term follow-up data and additional experience with this procedure are required. Autologous stem cell transplantation may limit the long-term toxicity of therapy in childhood SLE.
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PMID:Use of CD34+ autologous stem cell transplantation in the treatment of children with refractory systemic lupus erythematosus. 1566 87

There is accumulating evidence that mycophenolate mofetil (MMF), when combined with corticosteroid, is an effective induction treatment for severe proliferative lupus nephritis and is associated with fewer adverse effects compared to cyclophosphamide (CTX), but the quality of life (QOL) associated with these regimens as perceived by the patient has not been compared. This study included patients who had experienced both treatment regimens, for distinct episodes of diffuse proliferative lupus nephritis. QOL parameters during the first six months of each treatment were assessed through SF36 and WHOQOL questionnaires. Twelve patients and 24 episodes of severe lupus nephritis were studied. CTX-treated and MMF-treated episodes showed comparable baseline characteristics and response rate, with complete remission occurring in 83.3%. MMF treatment was associated with higher numerical scores for all domains across both QOL instruments than CTX. MMF treatment was associated with significantly less fatigue, less impediment of physical and social functioning, and better psychological well being compared to CTX. When each patient served as her/his own control, most patients ascribed higher QOL domain scores to the MMF-treated episode. Seventy-five percent of patients found MMF treatment more acceptable and preferred when compared with CTX, and the complications that most concerned them included Cushingoid features, alopecia, menstrual disturbance and infections. These data showed that MMF-based induction immunosuppression for severe lupus nephritis was associated with better QOL than CTX as perceived by patients, which was most likely attributed to the reduced side-effects during MMF treatment.
Lupus 2006
PMID:Quality of life comparison between corticosteroid- and-mycofenolate mofetil and corticosteroid- and-oral cyclophosphamide in the treatment of severe lupus nephritis. 1683 Aug 84

Childhood-onset systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease associated with significant morbidity and mortality with lupus nephritis being a major prognostic factor. Children with SLE tend to have more severe hematologic and renal involvement compared with adults. Although the morbidity and mortality have greatly improved over the last 20 years, recent studies show that there are still associated major risks from under treatment (with resultant severe flares of disease activity) and over treatment (with additional medication adverse effects including risks of severe infection; many of these patients have inherent abnormal complement pathways). Therapies used to treat children with SLE need to be individualized based on multiorgan involvement, severity of disease, history of disease flares, and knowledge of recent relevant clinical, hematologic, and immunologic parameters. These medications need to be the most effective treatments, allowing normal growth, development, fertility, and the avoidance of severe toxicity and future malignancies. Many toxic effects of current medications range from the well described Cushingoid features of corticosteroids to the gastrointestinal adverse effects of mycophenolate mofetil. In vitro studies have shown that rituximab causes B-cell depletion by mechanisms involving antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, and direct signaling leading to apoptosis. As the adverse effect profile of B-cell depletion with rituximab has been well described in adults and children with oncologic and other autoimmune diseases, initial pilot studies using rituximab in patients with refractory SLE have been carried out according to different protocols. Evidence to date in open studies demonstrates that targeted B-cell depletion therapy can be safe and efficacious as an addition to standard immunosuppressant agents in refractory childhood-onset and adult-onset disease. Although there are positive outcomes in using this therapy, caution is necessary with respect to minimizing the number of doses and treatments given to reduce the incidence of developing human anti-chimeric antibodies. The next phase for the clinical and research community are multicenter randomized controlled trials of rituximab in severe childhood SLE, such as a comparative trial of rituximab versus intravenous cyclophosphamide in patients both at presentation and with exacerbations of disease activity.
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PMID:Targeted B-cell depletion therapy in childhood-onset systemic lupus erythematosus: progress to date. 1805 7

A rare form of vascular disease in systemic lupus erythematosus (SLE), lupus vasculopathy is characterized by necrosis and accumulation of immunoglobulins (IGs) and complements in the wall of arterioles and small arteries resulting in luminal narrowing. Lupus vasculopathy often accompanies lupus nephritis and portends a poor prognosis. Although there is general agreement on the treatment of lupus nephritis, effective treatment strategies for lupus vasculopathy remain to be defined. We report a 20-year-old woman with SLE who presented with generalized tonic-clonic seizure. Her immunosuppressive regimen consisted of mycophenolate mofetil, prednisone and hydroxychloroquine. On physical examination, she was Cushingoid in appearance and hypertensive. Laboratory tests indicated renal disease. Coagulation studies disclosed de novo lupus anticoagulant. Magnetic resonance imaging of the brain demonstrated acute focal cerebral hemorrhage. Echocardiography revealed reduced ejection fraction and severe mitral regurgitation. Despite high-dose glucocorticoids and mycophenolate mofetil, renal function remained poor. Kidney biopsy demonstrated lupus vasculopathy and glomerulonephritis. Plasma exchange therapy and intravenous cyclophosphamide were administered. Over the ensuing four weeks, renal function improved, complement levels increased, autoantibody titers decreased and lupus anticoagulant disappeared. In conclusion, lupus vasculopathy can occur in SLE despite a heavy immunosuppressive regimen. Antiphospholipid antibodies might be involved in the pathogenesis of lupus vasculopathy. Plasma exchange therapy in conjunction with intravenous cyclophosphamide may represent an effective treatment strategy for lupus vasculopathy.
Lupus 2014 Apr
PMID:Lupus vasculopathy: Diagnostic, pathogenetic and therapeutic considerations. 2489 38

The treatment of SLE remains complex, and management is constrained by a lack of safe, effective, targeted therapies. Physicians, also, are constrained by a lack of evidence-based approaches with existing agents, including glucocorticoids, utilized in the majority of patients. While Cushingoid side effects of glucocorticoids are widely recognized, emerging literature now suggests that glucocorticoid use actually contributes to harmful outcomes in SLE, over and above these effects. These studies provide a compelling case for a re-evaluation of the long-term use of glucocorticoids in SLE, focusing on minimizing glucocorticoid exposure as part of the strategy to improve long-term outcomes. In this article, we review the evidence for the harmful effects of glucocorticoids in SLE, and propose therapeutic options that reduce reliance on glucocorticoids. We propose that it is time for the lupus community to have a louder conversation about glucocorticoid use, and for any residual complacency about their risk-benefit ratio to be banished.
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PMID:It hasn't gone away: the problem of glucocorticoid use in lupus remains. 2801 8

Glucocorticoids (GCs) have played a pivotal role in the treatment of immune-mediated inflammatory diseases (IMIDs) for a long time. However, GCs also incur a significant risk of undesirable adverse events such as Cushingoid changes, osteoporosis, glaucoma and metabolic abnormalities such as diabetes and hypercholesterolemia, which may lead to life-threatening cerebrovascular and cardiovascular events. High-dose GCs may also cause mental disorders and osteonecrosis. Recently, new therapeutic strategies have been developed to reduce the dose or even eliminate the need for GCs; multi-target drug therapies for systemic lupus erythematosus (SLE), biological agents such as tocilizumab and rituximab for systemic vasculitis, and anakinra and tocilizumab for adult-onset still's disease. Therefore, the era of GC-sparing or GC-free treatment for IMIDs is on the horizon.
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PMID:Era of steroid sparing in the management of immune-mediated inflammatory diseases. 3093 61

A 30-year-old female patient had been administered 5-mg/day prednisolone for systemic lupus erythematosus. She developed hypertension, dyslipidemia, moon face, central obesity, hypertrichosis, and impaired glucose tolerance. Although iatrogenic Cushing syndrome was initially suspected, we made a diagnosis of Cushing syndrome caused by a right adrenal adenoma, on the basis of the endocrine function test result and imaging findings. After surgery, the Cushingoid signs disappeared. Autoimmune diseases are often treated with corticosteroids; therefore, a differential diagnosis of primary Cushing syndrome should be made adequately.
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PMID:A case of systemic lupus erythematosus in which Cushing's syndrome caused by adrenal adenoma accidentally occurred during long-term maintenance therapy with corticosteroids. 3308 53