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Topical corticosteroids (TCSs) are a major part of the foundation of treatment for a wide variety of eczematous and inflammatory skin disorders in both adults and children. Mid-potency TCSs represent an important category as they are often used to treat eczematous dermatoses, such as atopic dermatitis. The TCS product must effectively release the active ingredient and promote cutaneous penetration so that therapeutic activity can occur. As many topical products eventually become available as generic formulations, it is important to recognize that although the active ingredient and its concentration are the same, the vehicle excipients may differ significantly, occasionally leading to potential differences in irritancy, in allergenicity, in effects on epidermal permeability barrier function, and, possibly, in efficacy. Clocortolone pivalate 0.1% cream is a mid-potency TCS formulated in an emollient formulation that has been shown to be effective and well-tolerated in the management of several corticosteroid-responsive dermatoses. This article outlines the pharmacologic and clinical data achieved with the original brand formulation of clocortolone pivalate 0.1% cream, and discusses the establishment of an authorized generic formulation that is identical in formulation to the original brand.

Midpotency topical corticosteroids (TCSs) are frequently used for the treatment of common eczematous and inflammatory skin disorders in both adults and children. There are several commercially available products in this category, and many vehicles and formulations for the clinician to choose from. Clocortolone pivalate 0.1% cream is a midpotency TCS formulated in an emollient formulation that has been shown to be effective and well tolerated when used appropriately in the management of several corticosteroid-responsive dermatoses. This article discusses the physiochemical properties of the compound; the characteristics of its emollient cream formulation; the functions of individual excipients; and the efficacy, tolerability, and safety data supporting its use in adults and children, including for facial involvement.

Objective: Study results evaluating the efficacy and safety of clocortolone pivalate 0.1% cream in the treatment of adults, young children, and infants with inflammatory facial dermatoses are reported in this article. Clocortolone pivalate 0.1% cream, indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses, is a mid-potency topical corticosteroid (Class 4) that has been studied and used extensively to treat a variety of corticosteroid-responsive inflammatory dermatoses, many of which often involve facial skin in both adults and children., Methods: Clocortolone pivalate 0.01% cream was applied to affected facial skin in subjects presenting with seborrheic dermatitis, contact dermatitis, atopic dermatitis, or psoriasis. Application was completed three times daily for 21 days. Assessments of erythema, edema, transudation, lichenification, scaling, pruritus and/or pain were completed at baseline and Days 4, 7, 14, and 21. Overall therapeutic response was assessed at all follow-up visits. Forty-nine subjects were entered, ranging in age from 1 month to 88 years of age. Thirty-eight subjects completed the studies, with 11 subjects lost to follow-up after the first visit. Individuals between the ages of 13 and 19 years were pre-emptively excluded to avoid potential application of a corticosteroid to acne-affected or acne-prone skin., Results: Treatment with clocortolone pivalate 0.1% cream resulted in decreases in erythema, edema, transudation, lichenification, scaling, and pruritus/pain in 76% of treated study subjects. The overall therapeutic response in approximately two-thirds of the subjects (68%) was rated as good to excellent. There were 7 adverse events noted over the course of the study that were judged to be related to treatment, all of which were cutaneous and localized to the site of application (acneiform eruptions, burning, and folliculitis)., Conclusion: Clocortolone pivalate 0.1% cream was effective in relieving the signs and symptoms of corticosteroid-responsive inflammatory dermatoses involving facial skin, including seborrheic dermatitis, contact dermatitis, atopic dermatitis, and psoriasis. Overall, the safety profile was favorable and devoid of any treatment-related serious adverse events.

Background: The aim of this study was to evaluate the efficacy of sole application of topical steroids after normal-risk keratoplasty., Patients and Methods: This randomized prospective clinical study assessed 40 patients who had undergone penetrating normal-risk keratoplasty. Twenty patients were treated exclusively with prednisolone acetate 1% eye drops 5x/day for 6 months postoperatively. Another 20 patients additionally received systemic fluocortolone 1 mg/kg body weight per day tapered within 3 weeks postoperatively. The main outcome measures included clear graft survival, ratio of graft rejection, and side effects., Results: The mean postoperative follow-up was 18+/-9 months. Three graft rejections were observed in the group receiving only topical steroids. Two graft rejections were observed in the group administered combined systemic and topical steroid therapy. None of the patients has developed irreversible graft failure so far., Conclusion: Sole topical steroid application seems to be an effective immune prophylaxis in patients undergoing penetrating normal-risk keratoplasty.

Hyperresponsiveness of the hypothalamo-pituitary-adrenal (HPA) axis in multiple sclerosis (MS), an autoimmune inflammatory disease of the central nervous system, is presumably due to diminished corticosteroid receptor function. It probably influences the immune response, but its clinical significance is not clear. Similar HPA dysregulation occurs in depression and is reversible with successful antidepressant treatment. We conducted a double blind, placebo-controlled trial to evaluate the neuroendocrine effect of cotreatment with the antidepressant moclobemide as an adjunct to oral corticosteroids in MS. Twenty-one patients with definite relapsing-remitting MS (11 females, aged 33.9 +/- 2.0 yr; Expanded Disability Status Scale score of neurological impairment, 2.0--6.5) in acute relapse were treated with placebo (n = 13) or 300 mg moclobemide (reversible monoamine oxidase A inhibitor; n = 8) for 75 days. All received oral fluocortolone from day 7 on, and the dose was tapered until day 29. Effects were evaluated using the combined dexamethasone-CRH test and clinically on days 1, 30, and 75. At baseline, the HPA axis was mildly activated, comparably for treatment groups [area under the curve for cortisol (AUC-Cort), 213.8 +/- 76.8 arbitrary units in the moclobemide group vs. 225.8 +/- 65.1 in the steroid alone group; mean +/- SEM]. In a group of healthy controls with comparable demographic characteristics, the AUC-Cort was 107.4 +/- 14.1. Moclobemide cotreatment resulted in normalization of the HPA axis response, whereas the HPA system hyperresponse was maintained with steroids alone (AUC-Cort on day 30, 85.9 +/- 22.8 vs.177.1 +/- 68.5; on day 75, 111.0 +/- 46.0 vs. 199.2 +/- 64.6). The change in Expanded Disability Status Scale was comparable for both groups. Although corticosteroids alone had no effect on the HPA response using the dexamethasone-CRH test, treatment with moclobemide combined with corticosteroids favors normalization of the HPA response in relapsing-remitting MS.

Background: Patients with severe scleritis who do not respond to high-dose corticosteroid therapy, or who require a daily corticosteroid maintenance dose higher than 30 mg prednisone should be treated by other immunosuppressants., Patients and Methods: In five patients with various types of severe anterior scleritis a long-term high-dose steroid treatment failed to control scleral inflammation. They therefore received cyclosporin (CsA). Follow-up was 16-26 months., Results: Scleral inflammation and ocular complications were controlled in all patients by a regimen of systemic CsA combined with a low maintenance steroid dose below the Cushing threshold. We observed no side effects under CsA serum levels of 120-150 ng/ml. In only one patient was scleral inflammation totally and lastingly eliminated., Conclusions: Systemic CsA therapy is of definite therapeutic value in the symptomatic management of steroid refractory severe anterior scleritis without associated systemic disease. Complete healing, however, is achieved only in a minority of cases.

The ubiquitous Mycobacterium avium-intracellulare (MAI) is the most frequent cause of disseminated atypical mycobacteriosis in AIDS patients. MAI infections may develop in patients with other acquired immune defects, such as connective tissue disorders. In adults, the gastrointestinal and respiratory systems are most frequently affected. We report a patient with dermatomyositis receiving immunosuppressive therapy in whom only the skin and the skeletal system were affected by MAI. Because it presented with polymyositis-like symptoms, the infection was initially not identified and treated. The MAI was cultured from a periarticular joint effusion from the right upper arm and from venous blood, as well as identified histologically in lesional skin. Resistance to antibiotics developed most likely because the patient failed to take oral antibiotics regularly. Because of an acute exacerbation of the tumor-associated dermatomyositis, immunosuppressive therapy was initiated, while the tuberculostatic therapy was continued. Using these therapies both diseases markedly improved. In patients with connective tissue disorders receiving longterm immunosuppressive therapy, especially when changes in symptoms and signs are observed, opportunistic infections such as MAI should be considered and included in the differential diagnosis.

Eleven patients with chronic sarcoidosis resistant to high-dose corticosteroids and other immunosuppressive treatments were treated with cyclosporine A at the initial daily dose of 5 mg per kg body weight (ideal weight in the case of overweight subjects) combined with flucortolone and methotrexate. A complete and lasting remission of the disease was obtained in all patients with total disappearance of pulmonary and extrapulmonary manifestations. In addition, the disease activity indexes normalized and remained normal for the rest of the follow-up period (24.82 +/- 8.22 months, range 12-33). No renal or hepatic toxicity was observed in any patient. Two of them presented hypertrichosis and one nausea.

Corticosteroids often induce a variety of psychiatric symptoms, such as alterations of mood, neuropsychological deficits and even psychotic states. To date, only a few studies have specifically addressed behaviour as well as cognitive functioning in patients under steroid treatment. Fifty ophthalmologic patients participated in this prospective study. They received methylprednisolone or fluocortolone at doses of 119 +/- 41 mg/day in the beginning and 75 +/- 22 mg after 8 days of treatment. Psychopathology and neuropsychological functioning were examined before and after steroid therapy, mood was self-rated on days 0, 3, 5 and 8. No marked psychopathological abnormalities such as psychosis, dementia or delirious states were observed. However, a significant proportion of patients suffered from an organic mood disorder, 26-34% experienced a hypomanic syndrome, 10-12% a depressive syndrome. Most neuropsychological tests did not reveal significant effects of steroid treatment. Performance of Word Fluency and Trail Making A improved, while the Auditory-Verbal-Learning and the Digit-Symbol showed a worsening. Psychopathological and neuropsychological effects were not significantly correlated.

Fluocortin butyl (FCB) is a recently developed topical intranasal corticosteroid that is inhaled as a powder and has been demonstrated to be well tolerated and to improve symptoms and signs of perennial rhinitis in previous short-term studies. This multicenter, open-label study evaluated the efficacy and safety of FCB during a 12-month treatment period in patients with perennial rhinitis. Treatment was initiated with one inhalation of FCB in each nostril three times a day (total dosage, 3 mg/day). In subsequent months, one third of the patients was maintained at the dosage of 3 mg/day, one third at a lower dosage of 2 mg/day, and the remaining one third of the patients at a larger dosage of 4 to 8 mg/day. Of 109 patients enrolled in the study, 90 patients (82.6%) completed all 12 months of treatment. Symptom and sign scores decreased significantly (p less than 0.001) at the 2-month evaluation compared to scores at baseline, and the improvement was maintained throughout the 12-month study period. After 12 months, greater than 80% of the patients had substantial control of symptoms. Specimens of nasal biopsies, performed at the beginning and end of treatment, revealed a decrease in eosinophils and other cellular infiltrates, a slight tendency of an increase in mast cell counts, and a trend toward normalization of the nasal mucosa. There were few adverse effects. Mean plasma cortisol levels were normal before and after corticotropin stimulation at baseline and after 12 months of FCB therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of daily subcutaneous injections of 5 different corticosteroids (15 mg/kg body weight) on the development of galactose opacities in young rats of approximately 60g body weight was investigated. Progress of cataracts was evaluated by planimetry of lens photos. The three glucocorticosteroids used (cortisol, prednisolone, fluocortolone) induced a slight acceleration of cataract development, while a mineralocorticoid (desoxy-corticosterone) caused a marked retardation. A temporary retardation was also observed with fluocortinbutyl, a rapidly metabolized steroid for topical use.

Nerisone cream (diflucortolon valerate 0.1%) has been clinically compared with fluocinolon-acetate on a double blind basis. The trial was carried out on 30 patients. The author comments that the results, in spite of some slight casuisties, appear to indicate a certain superiority of Nerisone cream when compared with the competitor's preparation.

The object of the present study was to investigate the clinical efficacy of Nerisona fatty ointment in very skin conditions. A total of 37 patients, most of them with chronic dermatoses, was treated. Either very good or good results were achieved in 100% of the cases. The side effects observed were very slight.

The side effects of corticosteroid therapy were studied in 50 children on long-term therapy for nephrotic syndrome or various collagen diseases. The treatment consisted of prednisolone given to 24 children, and Ultralan (6 alpha-fluor-16 alpha-methyl-1-dehydrocorticosterone) given to 15 patients, both in an alternate-day fashion. Both drugs as well as methylprednisolone and dexamethasone were given successively to 11 children. Duration of therapy and doses were equivalent in all patients studied. The patients on Ultralan therapy developed posterior subcapsular cataracts to a significant higher degree (10 out of 15) and more rapidly (after a cumulative dose of 5.0-10.0 g/m2 body surface area on 1-2 years duration of therapy) than on prednisolone monotherapy or on mixed steroid therapy.

In a randomized double blind study, we investigated the systemic effects of 3 different ointments containing corticoids. Every 7 patients out of a total of 21 patients suffering from various skin diseases were daily treated with 40 g of one of the 3 corticoid preparations over 8 days (group A: 0.05% clobetasol-17-propionate; group B: 0.25% fluocortolone trimethyl acetate; group C: 0.25% fluocortolone trimethyl acetate + 0.25% fluocortolone capronate). The plasma cortisol levels were determined by radioimmune assay. In group B and C, we did not observe any effect on the pituitary-adrenal axis, whereas in group A the plasma cortisol levels were extremely low already after 1 day of corticoid application. This adrenal suppression did not return to normal within 4 days after discontinuation of the corticoid. Our results suggest that highly potent topical corticoids are capable of adrenal suppression even without occlusive dressing and even in healthy persons.

Two patients with contact allergy to Ultralan preparations are reported. Each Ultralan preparation contains two of three related fluocortolone derivatives. The first patient reacted to all three derivatives. The second patient reacted to flucortolone and when retested 4 months later also to fluocortolone pivalate but ot to flucortolone caproate. The negative reaction to fluocortolone pivalate at the first examination was probably false negative due to a low test concentration. In order to avoid false negative patch test reactions the fluorinated steroids should possibly be applied in concentrations higher than 1%. No cross sensitivity to the other steroids for topical use was found.

Butyl 6alpha-fluoro-11beta-hydroxy-3,20-dioxo-16alpha-methyl-1,4-pregnadien-21-oate (fluocortin butylester, Vaspit) is a recently developed corticosteroid, its distinguishing properties being that it is non-embryotoxic and has practially no systemic effects. In the course of 6 multicentre studies fluocortin butylester was tested in the forms of cream, ointment and fatty ointment in a comparison with corresponding formulations containing fluocortolone (Ultralan) caproate or pivalate, or hydrocortisone acetate. The total study population comprised 1705 patients with various dermal disorders. The results of these double-blind contralateral studies permit the conclusion that the efficacy of the Vaspit preparations ranges between those of fluocortolone and hydrocortisone acetate. Considering the risks involved with local corticosteroid therapy in children the development of a local corticosteroid with the properties of fluocortin butylester must be acknowledged as an advance.

The acne-inducing effect of butyl 6alpha-fluoro-11beta-hydroxy-16alpha-methyl-3,20-dioxo-1,4-pregnadien-21-oate (fluocortin butylester, Vaspit) 0.75% was compared with that of hydrocortisone acetate 1.0% and diflucortolone valerate 0.1% in a model established by Plewig and Kligman. The steroid and the cream base uniformly used in all preparations were applied to the backs of 20 volunteers over 4 weeks. Dome-shaped red papules developed in the third week of occlusive treatment, and were counted in an area of 16 cm2 at the maximum of their development and graded according to a scale. The degree of papulation under diflucortolone valerate 0.1% was 2.15+/-0.75. No differences were observed between fluocortin butylester 0.75% (0.2+/-0.42), hydrocortisone acetate and the cream base (0.15+/-0.37).

A double-blind, half-side comparative dermal atrophy study of fluocortin butylester 0.75% clobetasone butyrate 0.05%, hydrocortisone acetate 1% and placebo creams was carried out in 29 healthy human male volunteers. Skin thickness was measured by a modified radiographic technique before and after an 8-week application period of the test preparations. Significant skin thinning occurred in 3 of the 10 subjects treated with clobetasone butyrate and atrophy of marginal significance in 1 of the 29 subjects treated with fluocortin butylester. The results suggest that, compared with other fluorinated topical steroids, fluocortin butylester 0.75% is unlikely to produce significant dermal atrophy when used in the short and medium term.

Twenty-one patients suffering from different autoimmune diseases (14 from systemic lupus erythematosus, 4 from rheumatoid arthritis, one from Sjögren's syndrome, one from systemic hypersensitivity vasculitis, and one from diffuse proliferative glomerulonephritis) were treated with a combined immuno-suppressive regimen. Cyclosporin was given at a dose of 5 mg/kg/day together with steroids. In addition, the rheumatoid arthritis patients also received methotrexate. In all patients a kidney biopsy was performed after a treatment period of 17 to 42 months (mean duration 21.7 months). The cumulative cyclosporin dose at the time of biopsy varied from 1.071 to 4.587 mg/kg. Patients suffering from systemic lupus erythematosus and rheumatoid arthritis were assessed according to a scoring system set up for this purpose. The combined therapy proved useful in these patients as reflected in the diminution of the respective activity scores, improvement of kidney function, and diminution of proteinuria. Histological examination of the kidney biopsy specimens showed only minimal activity in patients with systemic lupus erythematosus. No unequivocal signs of renal toxicity could be detected. In the last group, the condition of the patient with Sjögren's syndrome was stabilized and the patient with systemic vasculitis improved clinically. Neither patient had signs of kidney lesions. The patient with diffuse proliferative glomerulonephritis, in whom kidney biopsy was performed before and after treatment, showed improvement of kidney function, diminution of proteinuria, and diminution of inflammatory activity within the kidney, and no signs of cyclosporin toxicity.

The new corticosteroid diflucortolone valerate was clinically investigated in an international, multi-centre trial by a total of 162 dermatologists in 22 countries in more than 6,285 patients with inflammatory and allergic skin diseases. Depending on the condition of the skin, diflucortolone valerate was applied as a cream, ointment or fatty ointment at a concentration of 0.1%. Most of the patients treated with the cream displayed weeping skin conditions. The ointment was used mainly in patients with neither weeping nor very dry skin conditions, while the fatty ointment was employed mainly in very dry processes. After the exclusion of invalid record forms, 5,578 cases remained for computer evaluation. The results confirm that the success rate in local corticoid therapy can be improved by adapting the base to the respective skin condition. The forms investigated were found to be highly effective preparations with excellent skin tolerance. They can be placed on a par with today's leading topical corticoid preparations.

The mechanism of glucocorticoid-induced hypertension is not clarified. Recent data suggest an alteration of active electrolyte transport systems by glucocorticoids. We therefore studied the activities of the Na-K pump by measuring the Na-K-ATPase activity in erythrocyte ghosts and the ouabain-sensitive uptake of rubidium in erythrocytes of patients with Cushing's syndrome and of patients with exogenous glucocorticoid excess after treatment with fluocortolone or ACTH. Na-K-ATPase activity was significantly increased in patients with Cushing's syndrome and in patients treated with ACTH compared to the controls. Similarly, total uptake of 86Rb and the ouabain-sensitive uptake in erythrocytes were found to be above the control range both in patients with Cushing's syndrome and in patients treated with fluocortolone. There was no difference in furosemide-sensitive uptake of 86Rb. The results demonstrate an increased maximal activity of the Na-K pump in patients with glucocorticoid excess.

Two cases of encephalitis due to Listeria monocytogenes with lethal outcome are presented. The infection occurred during immunosuppressive treatment for panarteritis nodosa and sarcoidosis, respectively. The pathological-anatomical findings were a diffuse purulent meningoencephalitis in the first case and a focal rhombencephalitis with necrotizing inflammation of brainstem and cerebellum in the second one. Listerial infections of the adult are gaining increasing importance as severe complications of immunosuppressive treatment.

A 36-year-old man suffered from diarrhoea for some weeks and was treated with Salazosulphapyridie and Fluocortulon when he developed a transient myopia combined with an angle closure glaucoma. The refraction of his mild hyperopic eyes (+0,5 dpt) changed to -5,5 dpt and the intraocular pressure increased to 40 mm Hg in the right and 42 mm Hg in the left eye. Accommodation and pupillary reflexes were normal. Ultrasonic examination showed an increased axial diameter and a forward shifting of the lens. The resulting flattening of the anterior chamber induced the angle closure glaucoma. All symptoms disappeared within a week after the administration of Fluocortulon had been discontinued.

We report the results of a controlled double blind assay of treatment in 51 dermatologic cases, with a new steroid cream (diflucortolone) and an already known one (flumetasone). The diflucortolone valerate was significantly better than the flumetasone pivalate in the treatment of 16 cases of psoriasis, 33 eczemas and two cases of lichên planus.

The phototoxic action of ointment and fatty ointment of butyl 6alpha-fluoro-11beta-hydroxy-16alpha-methyl-3,20-dioxo-1,4-pregnadien-21-oate (fluocortin butylester, Vaspit) was examined by means of the epicutaneous test with subsequent UV-irradiation (Kromeyer lamp with Schott filter DG 18) in 20 patients with skin disorders. Photoallergic effects of fluocotrin butylester cream, ointment and fatty ointment were tested in a modified Draize test in which 198 subjects with normal skin participated. The subjects were sensitized in 10 epicutaneous tests conducted at intervals of 24 h and followed by irradiation (1500 W xenon lamp) with 2 MED. Treatment and irradiation were then repeated after a 2-week interval. This proceding permitted additional statements an phototoxicity of the administered preparations. No positive reactions occurred in either of the tests so that phototoxic effects can be excluded and a photoallergic potential is improbable.

A 45-year-old patient developed squamous cell carcinoma 4 years after renal transplantation and immunosuppressive therapy with azathioprine and fluocortolone. During the following 3 years, the patient developed on sun-exposed skin several premalignant hyperkeratoses, Bowen's carcinoma, basal cell carcinoma, as well as squamous cell carcinoma and carcinoma of the eccrine sweat glands, both showing the clinical picture of keratoacanthoma.

Plasma cortisol levels and the response of the adrenal gland to 0.25 mg ACTH administration were measured in 12 patients receiving 15 mg or more of a short-acting steroid (fluocortolone or prednisone) on three out of four days, in 10 patients on daily steroid treatment (15 mg prednisone or more per day), and in 9 normal subjects. The basal plasma cortisol level of the first group was between that of patients on daily prednisone treatment and that of normal subjects. The adrenal function in patients on the three out of four day treatment schedule appeared to be slightly diminished, yet still within the accepted limits for adrenals capable of responding adequately to stress. The adrenal function proved insufficient in all patients on daily steroids. The three out of four day steroid regimen thus offers a solution with many advantages over continuous steroid treatment for patients refractory to the alternate-day schedule.

Four patients with severe aplastic anemia were treated with a combination of cyclosporin (5 mg/kg/day) and steroids (prednisone 0.2-0.8 mg/kg/day 3/4 days). A positive response (transfusions stopped, granulocytes greater than 1500/mm3, thrombocytes greater than 50,000/mm3) was achieved in three of these patients. The therapy had a rapid effect on reticulocytes and granulocytes (7-14 days) while platelet numbers took longer to correct (2-4 months). All patients presented signs of dyserythropoiesis with macrocytosis. Side effects of therapy were minor (tremor, water retention, gynecomastia, hirsutism). In this series, the combination of cyclosporin with steroids appears to be an effective treatment for severe aplastic anemia with a more rapid result and better tolerance in comparison to antilymphocyte serum.

The development of glaucoma and amaurosis in a 29-year-old woman with atopic dermatitis is described. The association of the eye involvement with many years of daily application of fluorinated corticosteroid ointment to the eyelids is suggested.