Comparison of inhaled corticosteroids

OBJECTIVE: To review the comparative studies evaluating both efficacy and safety of inhaled corticosteroids in the management of asthma. Specifically, comparative clinical trials are evaluated that allow clinicians to determine relative potencies of the various inhaled corticosteroids. METHODS: A critical review was performed of the published clinical trials, either as articles or abstracts, comparing the clinical efficacy or systemic activity of inhaled corticosteroids. No a priori criteria were applied, as this was not a meta-analysis. FINDINGS: In vitro measures of antiinflammatory activity of corticosteroids consistently demonstrate potency differences among the various corticosteroids. Traditionally, these in vitro measures have been used to develop new corticosteroids with greater topical activity. While no accepted direct measure of antiasthmatic antiinflammatory activity exists, clinical trials using surrogate measures (e.g., forced expiratory volume in 1 second, peak expiratory flow, bronchial hyperresponsiveness, symptom control) indicate that in vitro measures provide a relatively accurate assessment of antiasthmatic potency. The relative antiinflammatory potency of the inhaled corticosteroids is in the following rank order. flunisolide = triamcinolone acetonide < beclomethasone dipropionate = budesonide < fluticasone. Studies of systemic activity appear to confirm this relative order of potency. Currently, no evidence exists for greater efficacy for any of the inhaled corticosteroids when administered in their relative equipotent dosages. The preponderance of current data suggests that when administered in equipotent antiinflammatory doses as a metered-dose inhaler plus spacer or as their respective dry-powder inhaler, the existing inhaled corticosteroids have similar risks of producing systemic effects. CONCLUSIONS: Delivery systems can significantly affect both topical and systemic activity of inhaled corticosteroids. More direct comparative studies between agents are required to firmly establish comparative topical to systemic activity ratios. The preponderance of evidence suggests that the agents are not equipotent on a microgram basis.     

Systemic side effects of external corticoids: results of dermatologic studies in children with neurodermititis

Of 111 children with atopic dermatitis who were admitted as in-patients in a German aero-biological childrens clinic, 83 patients (74.8%) had been prescribed a prolonged corticosteroid therapy from their family doctor. For 60 children (54.1%) the corticosteroid application was topital, partly with occlusive dressing or with fluorinated preparations. The remaining 23 children (20.7%) were treated topically and systemically with corticosteroids. Of the 60 children whose atopic dermatitis was treated exclusively with topical corticosteroids, 59 patients (98.3%) showed undesirable side effects. Moreover, irreversible body changes developed through the transcutaneous absorptive processes, which were more evident and appeared more often in girls than in boys.     

Use of Biobrane after laser resurfacing

BACKGROUND: Laser skin resurfacing has become an ever more popular and effective technique for the treatment of photoaged skin. Often a prolonged postoperative healing period adversely affects patients and physician satisfaction. Erythema and a certain degree of patient discomfort are often believed to be inevitable as they are thought to reflect depth of wounding and consequently the efficacy of wrinkle removal. In addition, a high incidence of irritant contact dermatitis has been observed, complicating recovery. OBJECTIVE: To develop a simplified wound dressing protocol aimed at achieving mild, short-term erythema and minimal side effects following effective rhytidectomy performed by laser resurfacing. METHODS: In a retrospective study from September 1995 to May 1997, 85 patients undergoing laser resurfacing for rhytid removal were placed on a postoperative wound care protocol consisting of immediate postsurgical once-only application, for 6 days, of Biobrane, a biosynthetic semipermeable dressing followed by the topical use of only a 10% cartilage extract in ointment. RESULTS: Thirty-eight full-face/three-quarter face, 26 supralabial, 13 perioral, and eight lower eyelid/crow's feet cosmetic units were treated. The fine and course wrinkles were improved in most patients, comparing favorably with other reported series. In 94% of patients erythema was absent to light pink at 4 weeks. Mild pain necessitating a medication was used in only five patients. Twenty-six patients developed transient hyperpigmentation and three patients developed focal hypopigmentation. Delayed irritant contact dermatitis presented in three patients. No infections developed and no scarring was observed. CONCLUSION: With this wound healing protocol, carbon dioxide laser skin resurfacing can effectively improved facial rhytids with minimal to insignificant erythema or discomfort.     

Onychomycosis

The prevalence and clinical types of onychomycosis and diagnostic methods are reviewed in this article. The need for correct identification of the causative organism is emphasized. The use of oral and topical therapeutic agents is outlined, with specific emphasis on relevant research data and potential side effects of these agents. Sections on the potential hazard of nail dust, onychomycosis in HIV-infected patients, and the long-term management of onychomycosis are also included.     

Contact allergy to topical corticosteroids and systemic contact dermatitis from prednisolone with tolerance of triamcinolone

We report the case of a 27-year-old female who had an allergic contact dermatitis to topical corticosteroids belonging to the corticosteroid groups A and D. Upon oral treatment with prednisolone a disseminated exanthema began within 24 h. Patch tests revealed sensitization to corticosteroids of group A, C and D, including prednisolone-21-acetate and betamethasone valerate, but not of group B corticosteroids such as triamcinolone. After intradermal testing of corticosteroids the exanthema flared again and the patient was treated with oral triamcinolone, with rapid improvement of her symptoms. A literature review revealed that exanthematous reactions after systemic treatment with corticosteroids have been rarely reported. Since corticosteroids are essential emergency drugs, a safe corticosteroid should be identified for such patients. Patch and intradermal tests may be used for that purpose.     

TARS. Their role in the treatment of psoriasis

The clinical experience reported by these studies does not definitively answer the question of whether or not all or even most tars are effective in the treatment of psoriasis. Information supports both views. With the present data, the following statements seem appropriate: 1. Tar alone may be helpful for a subset of individuals with mild to moderate psoriasis. Because the majority of patients with psoriasis have less than severe disease, this group numerically represents the majority of office-treated patients. For these patients, tars are not unreasonable to use in appropriate clinical circumstances. 2. Crude coal tar is not likely more beneficial than modified tar or gels. These latter preparations have much better patient acceptance and compliance because of decreased odor, staining, and messiness. 3. Overall, the potential severity of side effects from tars is less than that from anthralin and much less than that from topical corticosteroids (atrophy, rebound). 4. Clinical experience confirms that tar preparations can be effective when other modalities fail or cannot be used for reasons of adverse effects or otherwise. 5. Tar shampoos are considered useful therapeutic agents for active clearing therapy and for maintenance. 6. When combined with suberythemogenic ultraviolet light B, tar can be a useful agent. It has fewer side effects in terms of burning and irritation than does aggressive ultraviolet B therapy alone. The effect of maximal erythemogenic ultraviolet light B therapy is not enhanced with tar. Practically speaking, however, the majority of psoriatic patients do not require, or are not able to avail themselves of, convenient controlled ambulatory ultraviolet light therapy.     

15N investigation into the effect of a pollutant on the nitrogen metabolism of Tetrahymena pyriformis as a model for environmental medical research

The therapy of atopic dermatitis remains a challenge. The success of any therapeutic concept is based on a broad and early diagnostic approach which allows to rule out relevant provocation factors and allergens. During remission periods the regular use of a topical basic therapy consisting of drug-free emolients is recommended. Topical corticosteroids as well as systemic or local antimicrobial therapy and antihistamines are essential during periods of acute exacerbations. Although during the last years a great number of new therapeutic approaches have been published, data of most of these therapeutic modalities are not sufficient to allow an unrestricted use in all patients with atopic dermatitis.     

Topical NSAIDs for musculoskeletal conditions. A review of the literature

In recent years a growing number of topical nonsteroidal anti-inflammatory drugs (NSAIDs) have become available. This has been prompted in large part by the high incidence of serious gastrointestinal adverse events associated with the use of systemic NSAIDs, and the premise that minimisation of plasma concentrations of active drug may result in fewer systemic adverse effects. Evidence in humans and animals with topical NSAIDs demonstrates lower plasma concentrations than with systemically administered drugs, while those in soft tissues are still of a magnitude considered consistent with exerting an anti-inflammatory effect. In joints, however, the evidence is less strong, and there is still dispute whether in this case the drug reaches the joint predominantly via the transcutaneous or systemic route. There has been a sufficient number of studies of soft tissue conditions to demonstrate the superiority of topical NSAIDs over placebo and to suggest equivalent efficacy in comparison with some oral NSAIDs. For arthropathies, however, the literature is more sparse. Although several studies claim a benefit for topical NSAIDs against placebo, the results are less conclusive and further study is required. Trials of topical agents against intra-articular corticosteroids and rubefacients are either lacking or inconclusive. The adverse event profile of topical agents is reasonable: minor cutaneous effects occur in up to 2% of patients but tend to be self-limiting. Gastrointestinal events appear from the existing literature to be infrequent and minor, although long term studies are required. Bronchospasm and renal impairment have been reported and may be more frequent in patients who have experienced these effects with oral agents. The initial costs of topical agents tend to be higher than those of oral agents but a cost-effectiveness analysis suggests an overall benefit: this issue requires further clarification.     

Nonsurgical repigmentation therapies in vitiligo. Meta-analysis of the literature

OBJECTIVE: To assess the effectiveness and safety of nonsurgical repigmentation therapies in localized and generalized vitiligo by means of a meta-analysis. DATA SOURCES: Computerized searches of bibliographic databases, a complementary manual literature search, and contacts with researchers and pharmaceutical firms. STUDY SELECTION: Predefined selection criteria were applied to both randomized and nonrandomized controlled trials. DATA EXTRACTION: Two investigators independently assessed the articles for inclusion. When there was a disagreement, a third investigator was consulted. DATA SYNTHESIS: Sixty-three studies were found on therapies for localized vitiligo. Of these, 10 of 11 randomized controlled trials and 29 of 110 patient series were included. One hundred seventeen studies on therapies for generalized vitiligo were found. Of these, 10 of 22 randomized controlled trials and 46 of 231 patient series were included. Among randomized controlled trials on localized vitiligo, the pooled odds ratio vs placebo was significant for topical class 3 corticosteroids (14.32; 95% confidence interval [CI], 2.45-83.72). In the patient series, topical class 3 and class 4 corticosteroids carried the highest mean success rates (56% [95% CI, 50%-62%] and 55% [95% CI, 49%-61%], respectively). Side effects were reported mostly with topical psoralen and intralesional and class 4 corticosteroids. In the randomized controlled trials on generalized vitiligo, the odds ratio vs placebo was significant for oral methoxsalen plus sunlight (23.37; 95% CI, 1.33-409.93), oral psoralen plus sunlight (19.87; 95% CI, 2.37-166.32), and oral trioxsalen plus sunlight (3.75; 95% CI, 1.24-11.29). In the series, the highest mean success rates were achieved with narrowband UV-B (63%; 95% CI, 50%-76%), broadband UV-B (57%; 95% CI, 29%-82%), and oral methoxsalen plus UV-A therapy (51%; 95% CI, 46%-56%). Oral methoxsalen plus UV-A was associated with the highest rates of side effects. No side effects were reported with UV-B therapy. CONCLUSIONS: Class 3 corticosteroids and UV-B therapy are the most effective and safest therapies for localized and for generalized vitiligo, respectively.     

Smooth-muscle hamartoma of the tunica dartos of the scrotum: report of a case

Corticosteroids are effective in bringing about a clinical remission in patients with ulcerative colitis. However, in severely relapsed cases, corticosteroids are not always effective even when a high dosage is administered. In addition, the long-term use of corticosteroids often causes serious side effects. Therefore, an alternative treatment for active ulcerative colitis is necessary in order to avoid these clinical problems. In the present pilot study, the efficacy of leukocytapheresis using a centrifugal procedure was evaluated for corticosteroid-resistant, active ulcerative colitis. Fourteen patients with corticosteroid-resistant severely active ulcerative colitis were treated by leukocytapheresis. Thirteen patients (92.9%) achieved clinical remission within 4 weeks after the apheresis, and remained in remission for 8 months on average without any additional corticosteroid therapy. In the remaining patient, in whom remission was not induced, a total colectomy was performed immediately after the fourth course of leukocytapheresis. No significant side effects were noticed throughout the therapy. Both colonoscopic and histological examinations confirmed the beneficial effect of this procedure in terms of the reduction of severe inflammation of the affected colon. We found that the expression of two adhesion molecules, L-selectin and VLA4a, on the surface of peripheral leukocytes was decreased after this new therapy.     

Sedative effects of antihistamines: safety, performance, learning, and quality of life

Antihistamines are frequently part of the treatment regimen for seasonal and perennial allergic rhinitis occurring alone or in conjunction with associated airway disorders, such as asthma, sinusitis, and otitis media with effusion. These agents are also frequently prescribed for the treatment of urticaria to eliminate the need for long-term corticosteroids. This paper reviews the side-effect profile of the sedating and nonsedating agents (a classification given these drugs by the US Food and Drug Administration) in terms of patient satisfaction and quality-of-life parameters. Because the sedating antihistamines cross the blood-brain barrier more quickly and easily than the nonsedating antihistamines, they produce more central nervous system (CNS) effects, further exacerbating the decreases in decision-making, verbal learning, and psychomotor skills already experienced by the patient with allergic rhinitis. In contrast the now-preferred nonsedating agents do not readily cross the blood-brain barrier, do not produce CNS side effects, and, therefore, do not cause sedation or performance impairment. The nonsedating agents provide a safer alternative for patients with allergic rhinitis. Their use can increase patient satisfaction with the health care received.     

Systemic vascular resistance in intradialytic hypotension determined by means of impedance cardiography

Topical corticosteroids (TCS) are among the most frequently used topical therapeutics. Recently, it has been shown that TCS not only has antiproliferative actions, but also inhibits the differentiation of the epidermis and finally perturbates stratum corneum (s.c.) barrier function. It is well established that epidermal barrier function resides within the intercellular lipids of the SC. However, to date, little is known about the effects of TCS on the structure and composition of s.c. lipids. We therefore used hairless mouse skin to study the sequential changes of the s.c. permeability barrier and their intercellular lipids by ruthenium tetroxide staining and high-performance thin-layer chromatography (HPTLC) during topical use of corticosteroids. The results demonstrated a progressive increase in transepidermal water loss accompanied by a diminution in the SC intercellular lipid lamellae, which showed a normal structure of individual lamella. Analysis of lipid composition by HPTLC after a 6-week application of TCS also showed an obvious decrease in all the main components of s.c. lipids, which are known to constitute the permeability barrier of the skin. In light of these results, our work provides direct morphological evidence that TCS deteriorates the permeability barrier of epidermis when applied to normal skin.     

Beclomethasone dipropionate, budesonide and flunisolide in the treatment of bronchial asthma (a review of the literature and the authors' own research)

Inhalation corticosteroids (beclometasone dipropionate, budesonide, flunisolide) proved effective against bronchial asthma (BA) and safe as they induce no severe systemic side effects. Of these three drugs side effects arise most frequently in administration of beclometasone dipropionate, least frequently of flunisolide. These inhalation corticosteroids are indicated both in non-steroid-dependent and steroid-dependent BA to reduce the dose of oral steroids or, if possible, for their complete discontinuation. Flunisolide is the most potent and effective of all inhalation corticosteroids used in current practice.     

Allergic rhinoconjunctivitis treated with intramuscular injection of glucocorticoid

Effects and side effects of injectable depot steroid in the treatment of allergic rhinoconjunctivitis (hay fever) are described. A few controlled studies have shown injectable steroids to be superior to the effect of placebo and locally applied steroid. Over a period of 10 years from 1984-95 only 26 registered side effects were reported to the central Danish register for side effects of drugs (Laegemiddelstyrelsens Bivirkningsregister). Only eight concerned subcutaneous atrophy and in two cases the cutaneous changes persisted. Based on registration of number of treatments in the county of Funen 1996, it is estimated that the use of injectable depot steroids for treatment of hay fever accounts for about 535,000 DDD (defined daily doses corresponding to about 33,000 treatments per year). We conclude that the use of injectable corticosteroids in the treatment of hay fever is common and effective and side effects are very rare. However, injectable corticosteroids should only be used when conventional treatment is not sufficient to control symptoms.     

Differences in the management of inflammatory bowel disease in children and adolescents compared to adults

Managing IBD in children and adolescents requires attention to issues unique to these age groups. The spectrum of presenting signs and symptoms is broad and often, subtle. Physician awareness of intestinal and extra-intestinal features prompts earlier diagnosis and intervention. The focus of treatment is not limited to intestinal symptoms, but also involves assessing weight and height gains, sexual maturation, extra-intestinal manifestations and psychosocial well-being. Differences in selecting drugs for pediatric versus adult patients are based on: 1. lack of prospective trials establishing effective doses for different ages; 2. inability to swallow capsules; 3. importance of nutrition in promoting growth; 4. paucity of data regarding the long-term safety of medications; 5. untoward cosmetic effects of corticosteroids, and 6. the need to develop coping mechanisms for a chronic illness. While sulfasalazine and mesalamine are useful in mild disease, corticosteroids are necessary for moderate and severe disease. Metronidazole and ciprofloxacin are effective in perianal CD. Elemental and polymeric formulas induce and maintain remission in active CD and reverse growth failure. Immunomodulatory agents (azathioprine and 6-mercaptopurine) enable physicians to reduce steroids and hospitalization. In practice, combination therapy is recommended to control symptoms and limit drug-induced side effects.     

Is there a rationale for the drugs used in hair transplantation surgery?

BACKGROUND: Various medications may be used before, during, or after hair transplantation surgery (HTS) with the aims of maximizing patient comfort, reducing unwanted side effects, and improving the results of HTS. OBJECTIVE: The objectives of this study were to determine the current practice pattern and rationale for drug prescribing by a group of leading hair transplant surgeons and to review the literature for the evidence upon which these prescribing patterns were based. METHODS: A postal questionnaire was sent to 16 hair transplant surgeons from the United States and Canada, and the answers were analyzed. The relevant evidence-based literature concerning HTS was reviewed by medicine search. RESULTS: Questionnaires suitable for analysis were received from 14 of the surgeons. There were many differences in the pattern of prescribing drugs for the HTS procedure. There was general agreement about the use of local anesthetics but no consensus about the withholding of agents that might increase bleeding; the use of pre- and postoperative analgesics; the use of topical and systemic antibiotics; the use of corticosteroids; or minoxidil. Randomized controlled studies relating to these issues for HTS were not identified in the literature. CONCLUSION: A lack of consensus exists about the drugs used in HTS based on a lack of evidence-based medicine.     

Circulating skin-homing T cells in atopic dermatitis. Selective up-regulation of HLA-DR, interleukin-2R, and CD30 and decrease after combined UV-A and UV-B phototherapy

BACKGROUND: As the cutaneous lymphocyte-associated antigen appears to detect circulating T cells that migrate to the skin in atopic dermatitis but not T cells that migrate to mucosal sites in allergic asthma and rhinitis, we investigated T-cell activation markers and CD30 on the cutaneous lymphocyte-associated antigen-positive circulating T-cell subset in atopic dermatitis to see whether these markers are different from those in normal controls and related to disease activity. DESIGN: Open study. SETTING: University referral center. PATIENTS: Twelve patients with atopic dermatitis and 12 healthy controls. INTERVENTION: Combined UV-A and UV-B treatment for 2 months. MAIN OUTCOMES MEASURES: Percentage of circulating cutaneous lymphocyte-associated antigen-positive T cells that express HLA-DR, interleukin-2 receptor, CD69, CD71, and CD30 (triple-color flow cytometric analysis). Clinical score, Dermatology Life Quality Index, pruritus score, and consumption of topical corticosteroids were determined. RESULTS: Increased relative numbers of cutaneous lymphocyte-associated antigen-positive T cells expressing HLA-DR, interleukin-2 receptor, and CD30 were found in patients with atopic dermatitis before treatment. Treatment with UV-A and UV-B was associated with clinical improvement and a decrease of levels of HLA-DR, interleukin-2 receptor, and CD30 in cutaneous lymphocyte-associated antigen-positive T cells. HLA-DR on cutaneous lymphocyte-associated antigen-positive T cells correlated significantly with the clinical score. CONCLUSION: Expression of HLA-DR and interleukin-2 receptor is a sensitive marker of disease activity in atopic dermatitis. Apart from giving information on disease activity in atopic dermatitis, the availability of skin-seeking T cells in the blood offers the opportunity to obtain further information on T cells that may have effector function in the skin.     

Psychopharmacologic issues in organ transplantation. Part I: Pharmacokinetics in organ failure and psychiatric aspects of immunosuppressants and anti-infectious agents

This article discusses pharmacokinetics and pharmacodynamics during hepatic, renal, and cardiovascular insufficiencies. Hepatic metabolism of psychotropic drugs and of drugs commonly used in transplant patients that have neuropsychiatric side effects is discussed. Neuropsychiatric effects of immunosuppressant agents, including cyclosporine, corticosteroids, azathioprine, OKT3, and FK 506, are reviewed. Certain infections occur more often in immunosuppressed patients; their treatment with antiviral, antifungal, and antibiotic drugs may have neuropsychiatric consequences. Because of altered drug sensitivities and metabolism, drug interactions, and severe medical illness, most drugs are used in reduced doses.     

Acute myopathy associated with combined use of corticosteroids and neuromuscular blocking agents

OBJECTIVE: To review the occurrence and pathophysiology of myopathy associated with combined use of neuromuscular blocking agents (NMBAs) and systemic corticosteroids. DATA SOURCES: A MEDLINE search (1985 to July 1995, English language) yielded case reports and clinical studies involving myopathy or weakness associated with the use of NMBAs and/or corticosteroids. References cited in those articles were reviewed. DATA SYNTHESIS: Prolonged muscle weakness has been reported in intubated patients in the intensive care unit (ICU) who were receiving NMBAs and/or corticosteroids. Many cases involved the use of both agents in individuals with no underlying risk factors. The term "blocking agent-corticosteroid myopathy" (BACM) has been used to describe this myopathy when it develops following combined use of these agents. Features common to BACM include prolonged weakness, elevated creatine kinase concentrations, myopathic features on electromyography, normal nerve conduction and sensation, and reduced deep tendon reflexes. Muscle biopsy results vary, but tend to show type 1 and/or 2 fiber atrophy without inflammation. Some recently reported cases revealed thick myosin myofilament loss, which is consistent with findings in denervated rat muscle after exposure to corticosteroids. Two small prospective studies reported that 36-50% of mechanically ventilated patients receiving either one or both drugs developed prolonged weakness. CONCLUSIONS: NMBAs and corticosteroids alone have both been reported to cause myopathy in patients in the ICU. When coadministered, these agents appear to confer an even greater risk of myopathy; the exact pathology is not understood. Concomitant use of NMBAs and corticosteroids should be avoided if possible. Guidelines for cautious use and careful monitoring are suggested when combined use is deemed necessary.