SYSTEMIC LUPUS ERYTHEMATOSUS—Results of Treatment with Triamcinolone

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.     

Monthly plasmapheresis for systemic lupus erythematosus with diffuse proliferative glomerulonephritis: a pilot study

Twelve patients with systemic lupus erythematosus and biopsy-proved diffuse proliferative glomerulonephritis were randomly allocated to a control group (to continue receiving conventional therapy only) or to a plasmapheresis group (to receive conventional therapy along with one 4-I plasma exchange a month). The six patients treated with plasmapheresis had better preservation of renal function, reduced disease activity, fewer admissions to hospital and less need for steroid and immunosuppressive therapy than the six control patients. The patients treated with plasmapheresis also showed evidence of reduced immunologic activity and had no side effects attributable to the plasma exchange. These results suggest that monthly plasma exchange should be assessed in a controlled randomized trial as a possible therapeutic adjunct in patients with systemic lupus erythematosus and diffuse proliferative glomerulonephritis.     

PSYCHOSIS AND SYSTEMIC LUPUS ERYTHEMATOSUS—A Review of the Literature and Case Reports

In a review of the literature of the last 60 years concerning the association between psychosis and systemic lupus erythematosus, reports of 227 cases of this association were found. The average incidence of psychosis in the various series of systemic lupus erythematosus that were reviewed was 22 per cent. In only 25 per cent of the cases in which the information was given was the psychosis associated with steroid therapy.The psychiatric manifestations are variable and may be associated with a neurological disorder. Psychosis may antedate by many years other features of lupus. The psychosis due to lupus may respond to steroid therapy. Since systemic lupus erythematosus sometimes may be an important differential diagnosis of functional psychosis, appropriate diagnostic studies should be carried out in psychotic patients who have an accelerated sedimentation rate or positive serological test for syphilis without apparent reason.     

EXPERIENCES WITH ACTH AND CORTISONE IN SELECTED DERMATOSES

Fifty patients with various kinds of skin diseases who were not adequately relieved by conventional therapy were treated with ACTH or cortisone given systemically.Almost all patients with disseminated neurodermatitis had dramatic initial response, but in only about half the cases was improvement maintained when use of the drugs was discontinued.It appeared that in other skin diseases, such as lupus erythematosus, scleroderma, psoriasis, dermatomyositis and pemphigus, while improvement may be noted for a time, relapse to the original state occurs after the treatment is stopped.In four cases of chronic discoid lupus erythematosus, although some improvement was observed when steroid therapy was given, the histologic pattern of biopsy material taken from the lesions after treatment still was characteristic of the disease.     

Subcutaneous cystic granuloma caused byPhialophora verrucosa

A case of subcutaneous cystic granuloma caused byPhialophora verrucosa was reported. The patient was 21-year-old Japanese female with systemic lupus erythematosus (SLE) who had received prolonged steroid therapy. P. verrucosa has occasionally been isolated from patients as one of etiological agents of chromomycosis. There have been, however, no paper published to report an isolation of this fungus from subcutaneous cyst or abscess of a patient. This case is the first report of subcutaneous cystic granuloma induced clinically byP. verrucosa.     

Relative changes in the function of muscle ribosomes and mitochondria during the early phase of steroid-induced catabolism

1. Five glucocorticoids, when administered daily to rats for 5-7 days at a dosage of 5mg/kg, were in the following order of effectiveness with respect to their ability to decrease the weight gain of whole animals and the vastus lateralis, vastus medialis and gluteus medius muscles: corticosterone相似文献   

Ocular Complications of Chloroquine Therapy

Ocular complications of long-term chloroquine therapy were observed in 18 of 45 patients so treated. This therapy was used in patients with rheumatoid arthritis, lupus erythematosus, sarcoidosis, discoid lupus and other chronic “collagen disease”. Thirteen patients had reversible corneal opacifications, and seven had irreversible retinal changes, with visual loss and visual field defects. Pathological evidence of chloroquine retinopathy was obtained in one patient. Physicians are therefore warned to use this drug only after careful consideration. If it is used, repeated ocular examinations should include assessment of visual acuity, visual fields on a tangent screen and fundus examination through a dilated pupil.     

Lupus eritematoso sistémico en el anciano

Late-onset systemic lupus erythematosus (SLE) usually appears in patients older than 65 years and has clinical features different from the classical form observed in younger patients. In the elderly, SLE represents 10-20% of all SLE cases, shows a different and less aggressive clinical evolution and the first manifestations are non-specific. A significantly higher incidence of late-onset SLE in males, and the fact that postmenopausal women have a more benign disease, suggests that the estrogenic status may influence the activity of the disease. Owing to the insidious onset and the non-specific clinical manifestations on presentation, there is commonly a delayed diagnosis of late-onset SLE. Furthermore, the presence of comorbidities and concomitant therapies in elderly patients may limit the therapeutic options for SLE. The treatment of choice of joint symptoms and serositis includes non-steroidal anti-inflammatory drugs and low-dose steroids for short periods. In addition to the need for adopting a multidisciplinary approach, it is fundamental to obtain information about the functional, cognitive and social status of these patients in order to make appropriate healthcare decisions.     

Cyclophosphamide in Treatment of Systemic Lupus Erythematosus: 7 Years' Experience

This paper describes our experience with cyclophosphamide in the treatment of systemic lupus erythematosus. Since 1965 42 such patients have been treated either singly with cyclophosphamide or in combination with steroid. Serious complications have been rare except for amenorrhoea, which occurred in 14 out of 32 patients within the reproductive period. Our experience suggests that cyclophosphamide has an important, though not primary, part to play in the therapy of this disease.     

Relative potency in acute and chronic suppressive effects of prednisolone and betamethasone on the hypothalamic-pituitary-adrenal axis in man

The relative potency in the hypothalamic-pituitary-adrenal (HPA) suppression of both prednisolone and betamethasone was examined in an acute study with normal volunteers and in a chronic study with glucocorticoid-treated patients. Circadian rhythm of plasma cortisol was studied after a single dose administration of 5 to 30 mg prednisolone or 0.5 to 3.0 mg betamethasone at 8:00 hr. Morning-rise of plasma cortisol occurred on the morning after the administration of 30 mg or less prednisolone but no morning rise was noted after the administration of 1.0 mg or more betamethasone. Plasma ACTH was slightly elevated on the morning after 30 mg prednisolone administration but showed low levels throughout the night after 3.0 mg betamethasone administration. Plasma cortisol responsiveness to ACTH was examined in patients before and during therapy with either prednisolone or betamethasone. The basal cortisol level was not suppressed and the responsiveness to ACTH remained nearly normal during long-term 5 mg prednisolone therapy, but these were completely suppressed during long-term 5 mg betamethasone therapy. The responsiveness to ACTH was nearly normal in patients receiving alternate-day therapy with prednisolone in such large doses as 50 or 60 mg every other day, but was completely suppressed in patients receiving 1.0 mg betamethasone every other day. The relative potency of betamethasone in acute and chronic suppressive effects on the HPA system seems to be much stronger than that of prednisolone in equivalent doses with comparable anti-inflammatory effects. It is also suggested that the alternate-day therapy with such long-acting steroids as betamethasone are useless in preventing HPA suppression.     

SYNTHETIC ANTIMALARIAL DRUG THERAPY IN LUPUS ERYTHEMATOSUS AND POLYMORPHOUS LIGHT ERUPTIONS

The therapeutic efficacy of the synthetic antimalarial agents in lupus erythematosus and the polymorphous light eruptions is well established. Severe toxic reactions are rare but mild disturbances are relatively common. Although gold therapy probably is as effective in discoid lupus erythematosus, the antimalarials are easier to administer and cause fewer serious side effects. The mechanism of action of these drugs is poorly understood although definite anti-inflammatory properties have been noted. Perhaps further investigations of known biological processes such as free radical formation and neutralization, redox potential alterations or enzymatic changes may shed more light on this problem.     

Serum histidine-rich glycoprotein levels are decreased in acquired immune deficiency syndrome and by steroid therapy

Using radial immunodiffusion serum histidine-rich glycoprotein (HRG) levels were measured in acquired immune deficiency syndrome (AIDS) patients, in end-stage renal disease (ESRD) patients after renal transplantation and immunosuppressive steroid therapy, and in asthma and chronic obstructive pulmonary disease (COPD) patients treated with steroids. Compared with controls (12.5 +/- 3.0 mg/dl), HRG levels were significantly decreased in patients with AIDS (5.7 +/- 1.8 mg/dl, P less than 0.005): in patients with ESRD after renal transplantation with steroid therapy (4.4 +/- 1.1 mg/dl, P less than 0.005); and in asthmatic and COPD patients receiving steroids in acute (7.6 +/- 2.9 mg/dl, P less than 0.005) or chronic (7.4 +/- 3.0 mg/dl, P less than 0.025) high-dose regimens. In contrast, levels of hemopexin, another serum glycoprotein synthesized by the liver, were not lowered in these patients. These results show that serum HRG levels are selectively decreased in AIDS and in patients treated with immunosuppressive steroids.     

Acne conglobata; use of cortisone and corticotropin in therapy

Six patients with acne conglobata were treated with cortisone and adrenocorticotropic hormone. Definite immediate improvement was observed in all of them. In three cases control of the disease was maintained on relatively low doses of steroid. In one case there was response to superficial x-ray therapy after the acute phase of the disease had subsided in response to steroids. Resistance to steroid therapy apparently developed in one patient after approximately 18 months of treatment. One patient responded to treatment and then remained well (for two months when last observed) although steroids and all other treatment were discontinued. The combined use of antibiotics and steroids in the patients treated gave the best results.     

Studies on hormonal regulation of the growth of the craniofacial skeleton: IV. Specific binding sites for glucocorticoids in condylar cartilage and their involvement in the biological effects of glucocorticoids on cartilage cell growth

Using a whole-tissue binding assay and cell-free binding measurements indicated the presence of a specific steroid receptor for triamcinolone in cartilage cells of neonatal mouse mandibular condyle. Analysis of receptor levels showed that whole-tissue preparations bound 1360 fmol triamcinolone/mg protein. Affinity measurements revealed a dissociation constant of 7.6 X 10(-9) M. There was a close correlation between triamcinolone inhibition of DNA synthesis and steroid occupancy of whole-tissue receptors. The inhibitory effect of triamcinolone upon DNA synthesis could be significantly reduced by "blocking" the respective receptors with cortexolone. All the cartilage cells in the condyle revealed distinct intracellular labeling using [3H] dexamethasone autoradiography. Hence, neonatal condylar cartilage, an active site of endochondral bone formation in the craniofacial skeleton, can be regarded as a genuine target tissue for the biological effects of glucocorticoids.     

Enzyme activity of rat tibialis anterior muscle differs between treatment with triamcinolone and prednisolone and nutritional deprivation

The maximal activity of a selection of enzymes involved in muscle carbohydrate handling, citric acid cycle and fatty acyl beta-oxidation were studied after treatment with the fluorinated corticosteroid triamcinolone and compared to a similar treatment of the non-fluorinated corticosteroid prednisolone in an equipotent anti-inflammatory dose. Furthermore, because triamcinolone causes loss of body mass and muscle wasting, the effects of triamcinolone were investigated relative to a control group, with the same loss of body mass, due to nutritional deprivation. The study was performed in male Wistar rats in the following treatment groups: TR, triamcinolone treatment (0.25 mg x kg(-1) x day(-1) for 2 weeks), which resulted in a reduction of body mass (24%); ND, nutritional deprivation (30% of normal daily food intake for 2 weeks) resulting in a similar (24%) decrease of body mass as TR; PR, prednisolone treatment (0.31 mg x kg(-1) x day(-1) for 2 weeks), with a 10% increase in body mass; FF, free-fed control group, with a 12% increase in body mass in 2 weeks. Compared to FF, TR induced an increase in phosphofructokinase (PFK) activity (P < 0.01), glycogen synthase [GS(i + d)] activity (P < 0.05) and glycogen content (P < 0.01) in the tibialis anterior muscle. The PR and ND caused no alterations in PFK or citrate synthase (CS) activity compared to FF. Compared to PR, TR induced an increase in PFK (P < 0.01), CS (P < 0.05) and GS(i + d) activity (P < 0.01). Both TR and PR caused an increased muscle glycogen content, being more pronounced in TR (P < 0.05). Compared to ND, TR induced an increased CS (P < 0.05) and GS(i + d) activity (P < 0.01) and glycogen content (P < 0.01). The ND resulted in a decreased glycogen content compared to FF (P < 0.05). None of the treatments affected the activity of glycogen phosphorylase, beta-hydroxyacyl coenzyme A dehydrogenase and lactate dehydrogenase. It was concluded that corticosteroids led to an increased muscle glycogen content; however, the changes in the enzymes of carbohydrate metabolism were corticosteroid type specific and did not relate to undernutrition, which accompanied the triamcinolone treatment.     

Use of oral corticosteroids in the community and the prevention of secondary osteoporosis: a cross sectional study.

OBJECTIVE--To determine the prevalence of continuous use of oral steroids in the general population, the conditions for which they are prescribed, and the extent to which patients taking oral steroids are taking treatment to prevent osteoporosis. DESIGN--A cross sectional study with a four year retrospective review of drug treatment. SETTING--Eight large general practices in central and southern Nottinghamshire. SUBJECTS--A population of 65,786 patients (52% women) registered with a general practitioner during 1995. RESULTS--303 patients (65% (197) women) aged 12-94 years were currently taking "continuous" (for at least three months) oral corticosteroid treatment. This figure represents 0.5% of the total population and 1.4% (245/17 114) of patients aged 55 years or more (1.7% (166/9601) of women). The usual steroid was prednisolone (97% (294/303)), the mean dose was 8.0 mg/day, and the median duration of oral steroid treatment determined in 149 patients was three years. The most common conditions for which continuous oral steroids were prescribed were rheumatoid arthritis (23% (70)), polymyalgia rheumatica (22% (66)), and asthma or chronic obstructive airways disease (19% (59)). Only 41 (14%) of the 303 patients taking oral steroids had received treatment for the prevention of osteoporosis over the past four years. Although 37 of the 41 patients were women, only 10% (18/181) of the women over 45 years taking continuous oral corticosteroids were currently taking hormone replacement therapy. CONCLUSIONS--If our figures are typical then they suggest that over 250,000 people in the United Kingdom are taking continuous oral steroids and that most of these are taking no prophylaxis against osteoporosis.     

Flow cytometry analysis of glucocorticoid receptor expression and binding in steroid-sensitive and steroid-resistant patients with systemic lupus erythematosus

Introduction  

Glucocorticoid (GC) therapy is the main treatment for systemic lupus erythematosus (SLE). However, some patients are resistant to these agents. Abnormalities of glucocorticoid receptor (GR) seem to be related to steroid resistance. This study evaluated GRs in T lymphocytes and monocytes of SLE patients by flow cytometry (FCM) using a monoclonal antibody (mAb) and FITC-Dex probes.     

Macrolactonolides: A novel class of anti-inflammatory compounds

A new concept in design of safe glucocorticoid therapy was introduced by conjugating potent glucocorticoid steroids with macrolides (macrolactonolides). These compounds were synthesized from various steroid 17β-carboxylic acids and 9a-N-(3-aminoalkyl) derivatives of 9-deokso-9a-aza-9a-homoeritromicin A and 3-descladinosyl-9-deokso-9a-aza-9a-homoeritromicin A using stable alkyl chain. Combining property of macrolides to preferentially accumulate in immune cells, especially in phagocyte cells, with anti-inflammatory activity of classic steroids, we designed molecules which showed good anti-inflammatory activity in ovalbumin (OVA) induced asthma in rats. The synthesis, in vitro and in vivo anti-inflammatory activity of this novel class of compounds are described.     

Nitric Oxide Production Is Increased in Patients with Inflammatory Myositis

Nitric oxide (NO) production is increased in several inflammatory disorders. We have previously demonstrated higher levels of NO production among patients with rheumatoid arthritis and systemic lupus erythematosus. In this study we measured serum levels of nitrite and citrulline using calorimetric methods as surrogate markers of NO production among patients with inflammatory myositis (IM). Twenty patients with IM and 19 age- and sex-matched controls were studied. Serum nitrite levels were significantly higher among patients than among controls (986.6 +/- 880 and 204.3 +/- 113.9 nmol/ml, respectively; P = 0.001). Serum citrulline levels, too, were significantly higher among patients than among controls (3755.7 +/- 1905.5 and 189 +/- 177.2 nmol/ml, respectively; P < 0.0001). There was a positive correlation between steroid dosage and serum citrulline levels (r = 0.51, P = 0.036) and a negative correlation between steroid dosage and disease duration (r = -0.54, P = 0.025). It was concluded that NO production is increased in patients with IM and those with more active disease, as indicated by higher steroid dosage, have higher serum citrulline levels.     

Systemic Lupus Erythematosus Syndrome Induced by Practolol

Three patients with angina pectoris treated with practolol in varying doses developed a syndrome of arthralgia, particularly of the small joints of the hands, rash, fever, a raised E.S.R., and positive tests for lupus erythematosus (L.E.) cells and antinuclear antibody. The syndrome responded partly to withdrawal of the drug, but steroids were required to produce adequate symptomatic improvement. These disease features suggest that this is an example of drug-induced systemic lupus erythematosus (S.L.E.). The impaired ability of lymphocytes from these patients to transform in vitro indicates a testable hypothesis for the pathogenesis of the syndrome.