Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Seven patients with systemic lupus erythematosus (SLE), persistent thrombocytopenia (TP), in whom it was considered undesirable to institute an increase in steroid or immunosuppressive agents, were treated with danazol. Five patients completed the minimum period of 8 weeks. Two patients showed early response to danazol but were switched over to cyclophosphamide or azathioprine after 4 weeks because of systemic disease. Of the remaining five patients, four had complete responses. In one patient who failed treatment the TP was considered to be related to another drug (ranitidine). Other manifestations of SLE also improved with treatment. Side effects included amenorrhea in one patient, and hypoglycemia and hyponatremia in another. Infections were absent. Danazol can be a useful alternative treatment of lupus TP.
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PMID:Danazol in treatment of lupus thrombocytopenia. 180 60

A case of systemic lupus erythematosus (SLE) with subarachnoid hemorrhage due to a ruptured intracranial aneurysm is reported. A 31-year-old woman who had been treated with steroid for SLE was admitted to our department with severe headache, and nausea. CT scan showed subarachnoid hemorrhage and the left carotid angiogram revealed a small aneurysm at the supraclinoid portion of the left internal carotid artery. She had no neurological deficit. Hematological examination on admission showed disseminated intravascular coagulation (DIC), therefore, we decided to perform an intentionally delayed operation. In the meantime we treated the patient for DIC with FOY and methylprednisolone. The operation was performed after two weeks, when DIC had been eliminated completely. Postoperative hematological examination showed severe thrombocytopenia. We considered that SLE had come to the fore again, so we used Danazol in company with FOY and steroid. It seemed that Danazol was very effective for her. She was discharged about two months after admission with no problem. Cerebral apoplexy, such as cerebral infarction and cerebral hemorrhage, has often been seen in SLE, but subarachnoid hemorrhage due to a ruptured aneurysm is very rare. We could find only five reports of this phenomenon. Their prognoses were all, unfortunately, poor. It should be born in mind for therapy that a patient in SLE has a tendency to bleed. It seems that repeated hematological examinations and quick and proper management are important. We think that the aneurysmal formation in SLE is due to lupus vasculitis or the fragility of blood vessels due to a long use of Steroid.
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PMID:[A case of systemic lupus erythematosus with subarachnoid hemorrhage due to ruptured aneurysm]. 220 86

The purpose of the study was to determine if danazol was efficacious in the treatment of lupus MRL/MpJ (lpr) mice, as measured by longevity, proteinuria and serum amyloid protein (SAP) levels. Danazol, administered at an oral dose of 100 mg/kg, significantly prolonged survival of female MRL/MpJ (lpr) mice but had no effect on the mortality of their male counterparts. Medication with danazol began 40 days after birth of the mice and resulted in a significant decrease in proteinuria in female but not male lupus mice. The concentration of SAP, an acute phase reactant, was significantly decreased in danazol-treated female lupus mice at 80, 100, 120, 140 and 160 days of age when compared to vehicle-treated control mice. SAP levels in male lupus mice treated with danazol were significantly lower than normal control levels only at the 120 and 160 day time points. Measurements of mortality, proteinuria and SAP concentration indicate that danazol at 100 mg/kg is orally active in the treatment of MRL/MpJ (lpr) female, but not male mice.
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PMID:The effect of danazol in the MRL/lpr mouse model of autoimmune disease. 318 43

Although the etiology of lupus is imperfectly understood, immune factors, heredity, viral infections, and hormonal status are known to play a role. Studies of the sex ratio of lupus patients indicate that before age 10, twice as many girls as boys are affected, but after 12 years, 9.6 females are affected for each male. The incidence of lupus is almost constant for males of all ages but is much higher for women of fertile age than for other women. The deleterious effect of synthetic estrogens was 1st reported in 1966, and various studies since then have confirmed the results. The etiologic role of pregnancy is debated, but pregnancies can be successfully carried to term in periods of remission. Certain lines of mice spontaneously develop an autoimmune disease resembling disseminated lupus erythematosus. Anti-DNA antibodies appear earlier in the female and death from renal insufficiency occurs earlier than in males. Prepubertal castration does not influence the survival of female mice but significantly reduces that of males. Treatment with estradiol diminishes survival of castrated males and females, while treatment with androgens increases survival time of castrated to control females and of castrated males to that of control males. The timing and dose of treatment modify the response. Progesterone administered alone does not influence survival time of females but somewhat increases that of castrated males. Cyproterone acetate, an antiandrogenous progestin, has no effect in 2-3 week old males. Danazol, a moderately active androgen, has no effect on female mice. Nafoxidine, an antiestrogen, increases survival times. These results support the opinion that estrogens aggravate lupus while androgens have a protective effect. Different hormonal treatments have been prescribed for human lupus. Some beneficial effect for female patients has been observed with danazol, but the drug entails significant hepatic, metabolic, and hypertensive risks and may produce androgenic side effects such as voice modifications and hirsutism. Cyproterone acetate, a derivative of 17-hydroxyprogesterone, is without vascular and metabolic side effects and can halt ovarian function at a dose of 50 mg/day. It behaves as a peripheral antiandrogen and may have androgen agonist activity in some tissues. The mechanism of interaction of sex hormones in lupus may be explained by their influence on cellular and humoral immunity. Estrogens appear to suppress cellular immunity and stimulate humoral immunity, while androgens appear to play a suppressive role at the 2 levels. Contraception for women with lupus must be effective. Combined oral contraceptives and low-dose norsteroid progestins are contraindicated because of their thromboembolic and vascular risks. Low-dose progestins may be used but cause hyperestrogenism in some women. Chlormadinone acetate at a daily dose of 10 mg has no significant vascular effect. IUDs may have reduced efficacy during corticotherapy and pose a risk of infection. Only mechanical vaginal methods ose no threats for lupus patients, but they must be understood and accepted by the patient.
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PMID:[Hormones and lupus]. 391 21

Danazol therapy was used in the treatment of three consecutive patients with lupus-associated thrombocytopenia refractory to high-dose prednisone therapy (two patients) or in whom high-dose prednisone therapy was considered contraindicated (one patient). Treatment was associated in each case with an increase in platelet count but was complicated in two of three patients by the development of a diffuse maculopapular rash that promptly resolved following discontinuation of danazol therapy. Retreatment of one patient with danazol was associated with immediate recurrence of the rash. We suggest that danazol therapy deserves further evaluation in the treatment of lupus-associated thrombocytopenia, but advise that patients be carefully monitored for rash.
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PMID:Danazol for lupus thrombocytopenia. 407 40

We describe a patient with Primary Antiphospholipid Syndrome (PAPS) and severe thrombocytopenia with bleeding, in whom treatment with high dose steroids failed to maintain a sustained level of platelets following an initial short lived response. After several unsuccessful attempts with Danazol and aspirin combined with low dose steroids, the platelets count rose following the administration of chloroquine and low dose steroids and remained in the normal range even when steroids were tapered.
Lupus 1996 Feb
PMID:Correction of severe thrombocytopenia with chloroquine in the primary antiphospholipid syndrome. 864 33

The lupus anticoagulant may be accompanied by an acquired factor II deficiency and bleeding. We report on a patient with a lupus anticoagulant and factor II (Fll) deficiency responsive to Danazol. Acquired hypoprothrombinemia (FII) with the lupus anticoagulant (LA) may be accompanied by a hemorrhagic diathesis. A 64-year-old male with discoid lupus erythematosis bled after an intestinal polypectomy. His FII level was 18%, and his FII antigen level was 20%. Danazol (D) (600 mg per day) administration was associated with a rise in FII activity and antigen to 50% within 10 days. The patient underwent abdominal surgery. We studied the effect(s) of D on the FII level and on other coagulation factors in this patient. The patient's plasma FII antigen had a single precipitin arc compared to the two peaks of normal plasma on counterimmunoelectrophoresis with Ca++. The samples pre- and during D therapy had the same positively charged arc as normal samples, although they were quantitatively different. Neuraminidase treatment demonstrated a decrease in the positively charged migration of normal and the patient's FII antigen. Affinity chromatography of normal and patient plasma on a Sepharose protein A column revealed FII antigen present in the patient's bound fraction. The relative percentages of bound FII before and during D treatment were similar. During D therapy, levels of FIX and X rose 50-100%, and protein C rose 20-25%, while free protein S did not change. D is an effective therapy for acquired FII deficiency associated with LA. D does not affect the binding of Ig to FII, but D raises FII levels by increasing synthesis of the FII protein.
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PMID:Acquired hypoprothrombinemia: effects of danazol treatment. 894 70

Low endogenous levels of dehydroepiandrosterone (DHEA) and/or its sulfoconjugated derivative DHEA-S have been associated with diseases such as lupus, cancer, and diabetes. Circulating concentrations of DHEA and DHEA-S resulting from endogenous production or hormone supplementation may also be relevant in psychiatric illness. Drugs may significantly increase or decrease circulating concentrations of these adrenal androgens by various mechanisms. Some agents, such as dexamethasone, affect the HPA axis by inhibiting ACTH and therefore decrease DHEA and DHEA-S concentrations. Central nervous system agents, including carbamazepine and phenytoin, induce the P450 enzymes that metabolize DHEA and DHEA-S and therefore decrease circulating concentrations of these hormones. Danazol alters the ratio between DHEA and DHEA-S by inhibiting sulfatase. As research moves forward to better understand the relationships of these adrenal androgens with health and disease, it is essential that studies be designed to control for the influence of administered pharmaceuticals on DHEA and DHEA-S.
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PMID:The influence of hormones and pharmaceutical agents on DHEA and DHEA-S concentrations: a review of clinical studies. 1186 61

The purpose of this study was to compare the long-term effectiveness among danazol, corticosteroids, cytotoxics, and dapsone in the treatment of hematological manifestations of systemic lupus erythematosus (SLE). Medical charts of all patients seen at the Rheumatic Disease Unit from January to December of 1998 were reviewed. Patient characteristics, disease and treatment information were collected. The main outcome measures were the cause of and time to discontinuation of drugs used to treat hematological manifestations of SLE resulting from all causes, mainly toxicity and inefficacy or both. Bivariate analysis including one-way ANOVA and chi2 tests were used to compare differences between means and proportions, respectively. Survival curves among the different drugs were evaluated using the Kaplan-Meier method. Multivariate analysis (Cox-regression) was used to adjust for potential confounders. After all medical records were reviewed 41 cases were eligible. Two cases had hemolytic anemia, 34 had thrombocytopenia, and five had both. These cases had received a total of 121 cycles of treatment at different times and they represent the study population (corticosteroids n = 37, danazol n = 51, citotoxic drugs n = 29, and dapsone n = 4). Crude rates of discontinuations due to any cause, toxicity and inefficacy werenot statistically significant among the drugs. However, the Kaplan-Meier curves showed statistically significant difference for discontinuations due to all causes as well as inefficacy. Prednisone and cytotoxic drugs had the lowest probability of continuation. In contrast, there were not statistically significant differences among the drugs with respect to first relapse. This is the first study examining the long-term termination rates of several drugs used to treat hematological manifestations of SLE. Using rates of discontinuation adjusted for time there were statistically significant differences among the drugs. Danazol had the highest probability of continuation.
Lupus 2003
PMID:Long-term effectiveness of danazol corticosteroids and cytotoxic drugs in the treatment of hematologic manifestations of systemic lupus erythematosus. 1258 27