A systematic review of the safety of topical therapies for atopic dermatitis

BACKGROUND: The safety of topical therapies for atopic dermatitis (AD), a common and morbid disease, has recently been the focus of increased scrutiny, adding confusion as how best to manage these patients. OBJECTIVES: The objective of these systematic reviews was to determine the safety of topical therapies for AD. METHODS: Databases searched included: OVID Medline, Medline In-Process and Other Non-Indexed Citations, Embase, and the Cochrane Central Register of Controlled Trials. In addition to the articles identified by this search, investigators were also referred to a list of links (most recently updated 25 September 2005) to recent Food and Drug Administration (FDA) studies, reports and meetings regarding the topical calcineurin inhibitors for further potential references. Only fully published papers available in English and data obtained from FDA sites were included. Furthermore, the criteria for inclusion and exclusion for each systematic review were further evaluated at a meeting of all of the content and evidence-based medicine experts participating in this process and alteration of the inclusion criteria was done at that time when it was felt necessary to avoid inclusion of lower-quality data in the review. Qualitative review of the abstracted data was performed and reviewed at a meeting of all of the content and evidence-based medicine experts. RESULTS: While systemic exposure to these topical agents does occur, physiological changes appear to be uncommon and systemic complications rare and have only been found with use of topical corticosteroids. CONCLUSIONS: Based on the data that are available the overall safety of AD therapies appears to be good with the only documented systemic side-effects of therapy those occasionally seen with use of topical corticosteroids.     

Advances in management of atopic dermatitis: new therapies and novel uses of existing treatments

Atopic dermatitis (AD) is a chronic inflammatory skin condition marked by intensely pruritic, eczematous changes. First-line therapy includes topical corticosteroids during an exacerbation and long-term emollient use, followed by topical calcineurin inhibitors, phototherapy, and systemic therapy in more difficult cases. The need for more effective AD therapies with safer side effect profiles has pushed researchers to devise new therapies and to recycle traditional treatments for use in a novel manner. Innovative therapies include barrier therapy, novel antistaphylococcal treatments, new immunomodulatory agents, unconventional antipruritic agents, exclusionary diets, and probiotics. Advancements in these options have paved the way for a targeted approach to AD therapy. We will review the latest clinical research exploring these cutting-edge AD treatment modalities and discuss forward-thinking therapy strategies that use conventional AD medications in a novel manner.     

Dermatologists and Allergists Have Far More Experience and Use More Complex Treatment Regimens in the Treatment of Atopic Dermatitis Than Other Physicians

BACKGROUND: Atopic dermatitis (AD) is a prevalent skin condition, especially in the pediatric population. Whereas it has been shown that dermatologists prefer using more intensive therapy for AD than generalists, actual drug utilization has not been quantified. OBJECTIVE: The purpose of this study is to characterize visits for and treatment of AD in the office-based setting. METHODS: National Ambulatory Medical Care Survey data from 1990 to 1997 was analyzed to determine the use of topical corticosteroids (including their relative potencies), oral antibiotics, and oral antihistamines in the treatment of AD. RESULTS: There were an estimated 900,000 outpatient visits per year for AD. If in some visits to generalists the diagnosis for AD was miscoded as contact dermatitis, there may have been as many as 3 million outpatient visits per year for AD. Topical corticosteroids were used in 67% of visits with a mean potency rank of 4.5 (4.3, 4.8 95% CI). Dermatologists saw 48% of all visits for AD (63 yearly visits/physician) and allergists saw 10% of visits (30 yearly visits/physician). Other physicians saw from 0.1 to 2 yearly visits per physician. Dermatologists were the most likely to use topical corticosteroids (81% of visits) and high-potency corticosteroid agents (22% of visits). Dermatologists and allergists were the only physicians to prescribe ultrahigh-potent corticosteroid agents (12% and 9% of visits, respectively) and were more likely than other physicians to use multiple-agent regimens (21% and 27% of visits treated with a corticosteroid agent, respectively). CONCLUSIONS: Dermatologists and allergists have more expertise in the management of AD than other physicians, as suggested by their higher per capita visits and greater use of complex topical corticosteroid regimens.     

Atopic dermatitis: an update and review of the literature

Atopic eczema/dermatitis from the aspects of immunologic background, genetics, skin barrier dysfunction, IgE receptors, and triggers of AD (including allergens, microorganisms, and autoantigens) is described. Also reviewed are diagnostic procedures, treatment modalities with topical treatment (emollients, topical corticosteroids, topical calcineurin inhibitors, wet wrap therapy, and topical antimicrobial therapy), systemic management (antimicrobials, systemic corticosteroids, cyclosporine A, azathioprine, antihistamines), and phototherapy. Primary and secondary prevention are discussed and the role of the different cell receptors and their up-and down-regulation in this setting are emphasized.     

Selecting topical and systemic agents for recurrent aphthous stomatitis

Recurrent aphthous stomatitis (RAS) is one of the most common oral diseases worldwide. Although the exact etiology of RAS remains unknown, a variety of topical and systemic preparations may be used for palliation or prevention. In most patients with RAS, topical agents, including over-the-counter preparations such as amlexanox, prescribed corticosteroids, or antimicrobial agents, are sufficient to control the disease. Patients with frequent exacerbations or those with a severe form of RAS that is unresponsive to topical treatments often require systemic agents to control their disease. These include corticosteroids, colchicine, dapsone, pentoxifylline, and thalidomide. All therapies are palliative, and none result in permanent remission.     

Balancing efficacy and safety in the management of atopic dermatitis: the role of methylprednisolone aceponate

Although emollients can be sufficient to manage mild atopic dermatitis (AD), acute flares resulting in moderate‐to‐severe symptoms require treatment with anti‐inflammatory agents, such as topical corticosteroids (TCs) and topical calcineurin inhibitors (TCIs). This review examines the role of a member of the newest class of TCs, the fourth‐generation compound methylprednisolone aceponate (MPA) in AD management, with reference to the chemical structure, pharmacokinetics, efficacy in AD, safety assessed in preclinical and clinical trials and dosing considerations. MPA has an optimized efficacy/safety profile with minimal local or systemic adverse effects. In addition, it offers the opportunity for once‐daily dosing, which provides benefits in terms of patient compliance with treatment.     

Optimizing the treatment of atopic dermatitis in children: a review of the benefit/risk ratio of methylprednisolone aceponate

Atopic dermatitis (AD) is a chronic, recurring, pruritic, inflammatory skin condition which has its onset in early childhood in most cases. A stepped approach to therapy, starting with emollients and adding first mild and then more potent topical medications is recommended. For more than 50 years, topical corticosteroids (TCs) have been the gold standard in AD therapy. Increasingly potent TCs have tended to come with increasing risk of adverse events, however. Calculating the benefit/risk ratio [or therapeutic index (TIX)] for TCs when treating children and infants is more challenging in this population. Not only does their increased surface area to volume ratio as a result of their small size mean that they are likely to absorb a greater proportion of any active agent applied to their skin, but drug metabolism is slower than in adults and the systemic effects of corticosteroids are more pronounced (in particular reduction of serum cortisol levels through suppression of the hypothalamic–pituitary–adrenal axis). Unlike traditional TCs, topical calcineurin inhibitors are not associated with the systemic effects and have shown good efficacy in treating AD in children. Parental/Carer concerns about their long‐term use can limit their acceptance for treatment in the paediatric population, however. Modifications to the structure of fourth generation corticosteroids mean that increased potency is not accompanied by increased risk of adverse events and hence they have an improved TIX. Methylprednisolone aceponate is a potent fourth generation corticosteroid which has demonstrated efficacy and safety in acute and maintenance programmes in infants and children. It is licenced for once‐daily use, and is available in four formulations – ointment, fatty ointment, cream and milk, which combine with its improved TIX to meet the needs of young patients and their carers.     

Tacrolimus ointment: utilization patterns in children under age 2 years

Atopic dermatitis (AD) is a common eczematous skin condition; as many as 10-17 percent of all children are affected, and 35-60 percent of affected patients manifest symptoms manifest during the first year of life. Treatment principles for AD in young children involve conservative measures such as avoidance of hot water and environmental irritants, combined with liberal use of emollients after bathing. Low potency topical corticosteroids (TCS) are the current standard of therapy for AD in young children, reserving mid- and high-potency TCS for severe disease. However, complications of long-term use of TCS include skin atrophy, stria formation, telangiectasia, hypopigmentation, secondary infections, steroid acne, allergic contact dermatitis, and miliaria. The pediatric population is also at increased risk for systemic absorption because of their high ratio of skin surface to body mass. Systemic absorption may result in hypothalamic-pituitary-adrenal axis suppression and ultimately growth retardation. Although most topical and systemic corticosteroids are not approved by the Food and Drug Administration for use in children less than 2 years of age, conservative treatment often fails in this age group and frequently patients are treated with TCS, antibiotics, and antihistamines.     

Topical therapy in pediatric atopic dermatitis

With a prevalence of 10% to 20% in the first decade of life, atopic dermatitis (AD) is one of the most common skin disorders in young children. It is a chronic illness with limited therapeutic options. Topical anti-inflammatory agents remain at the core of medical management; however, their efficacy must be balanced with safety concerns, especially as they relate to the pediatric population. This article discusses the principles of topical AD therapy with a detailed review of the differences between topical corticosteroids and topical calcineurin inhibitors. It also includes specialized topical treatment strategies for AD, such as wet wraps and diluted bleach baths, and highlights the most common challenges to patient compliance in atopic dermatitis.     

Immunomodulation and safety of topical calcineurin inhibitors for the treatment of atopic dermatitis

Atopic dermatitis (AD) is a chronic or chronically relapsing inflammatory skin condition that primarily affects children. Topical corticosteroids have been the mainstay of treatment since the late 1950s. While providing excellent short-term efficacy, topical corticosteroid usage is limited by potential adverse effects, including impairment of the function and viability of Langerhans cells/dendritic cells. The recently introduced topical calcineurin inhibitors pimecrolimus cream 1% (Elidel) and tacrolimus ointment 0.03 and 0.1% (Protopic) exhibit a more selective mechanism of action and do not affect Langerhans cells/dendritic cells. For the immune system of young children 'learning' to mount a balanced Th1/Th2 response, this selective effect has particular benefits. In clinical experience, topical calcineurin inhibitors have been shown to be a safe and effective alternative to topical corticosteroids in almost 7 million patients (>5 million on pimecrolimus; >1.7 million on tacrolimus). Topical pimecrolimus is primarily used in children with mild and moderate AD, whereas tacrolimus is used preferentially in more severe cases. None of the topical calcineurin inhibitors have been associated with systemic immunosuppression-related malignancies known to occur following long-term sustained systemic immunosuppression with oral immunosuppressants (e.g., tacrolimus, cyclosporine A, and corticosteroids) in transplant patients. Preclinical and clinical data suggest a greater skin selectivity and larger safety margin for topical pimecrolimus.     

Oral supplements in atopic dermatitis

Atopic dermatitis (AD) is the most common chronic inflammatory skin disorder. The disease is typified by chronic pruritus, a series of signs and symptoms associated with immune dysfunction (eg, increased immunoglobulin E mediated allergies), and abnormal skin barrier dysfunction (eg, increased response to irritants). Due to the chronic itch and reactivity, patients and parents of affected children will seek therapy. Therapies range from emollients to topical medicaments, including topical corticosteroids, and immunosuppressive agents. Due to concerns about the side effects of the available agents, patients and their loved ones will often seek “natural” agents as therapy. Oral agents that have been tried in (AD) include probiotics, vitamins, oils, and such traditional therapeutics as Chinese herbals and Ayurvedic agents. At this time probiotics may be promising, but there are inadequate data to determine their efficacy. In addition, there are significant concerns for the risks associated with Chinese herbals, which may be associated with liver failure and death, and Ayurvedic agents, which may be tainted with heavy metals. The safest and most effective natural agents are topically applied emollients.     

Adherence to clocortolone pivalate cream 0.1% in a pediatric population with atopic dermatitis

Topical corticosteroids are first-line treatments for atopic dermatitis (AD) and their efficacy is well-established in randomized controlled clinical trials. When corticosteroids fail in clinical practice, it often is attributed to nonresponse. However, poor adherence also should be considered. With the advent of electronic monitoring systems, objective data on adherence can be obtained. The purpose of this study was to determine both self-reported and actual adherence to clocortolone pivalate cream 0.1% in the treatment of AD in a pediatric population. Six participants completed the 4-week study. Self-reported adherence was significantly higher than objectively measured adherence (P = .01). In general, adherence was best during the first week of treatment and tapered off thereafter. Clocortolone pivalate cream 0.1% was generally effective, with rapid improvement over the first week of treatment, even when adherence was limited. This study was limited by the small sample size and the failure of 2 participants to complete the study. Patients overestimate their adherence behavior. While some patients are adherent to treatment, others rapidly discontinue their use of medication over time. Midpotency topical corticosteroids such as clocortolone pivalate cream 0.1% are highly effective treatments for AD. Poor adherence should be considered when AD is not responding to topical corticosteroid treatment.     

Treatment outcomes of secondarily impetiginized pediatric atopic dermatitis lesions and the role of oral antibiotics

Patients with atopic dermatitis (AD) are predisposed to infection with Staphylococcus aureus, which worsens their skin disease; it has been postulated that the lack of antimicrobial peptides due to aberrant allergic inflammation in skin with AD could mediate this enhanced bacterial susceptibility. We sought to characterize the amounts of S. aureus and biological products found in infected AD lesions and whether treatment with topical corticosteroids and oral cephalexin as the only antimicrobial improved outcomes. Fifty-nine children with clinically and S. aureus-positive impetiginized lesions of AD were enrolled in this study. A lesion was graded clinically using the Eczema Area and Severity Index, and wash fluid was obtained from the lesion for quantitative bacterial culture and antibiotic sensitivities and measurement of bacterial products and cytokines. Subjects were re-evaluated 2 weeks after treatment. Improvement in the clinical and inflammatory characteristics of impetiginized lesions were noted, even in the 15% of lesions infected with Methicillin-resistant S. aureus (MRSA). In a subgroup of subjects whose lesions did not contain S. aureus 2 weeks after initiating treatment, beta-defensin levels were higher at both visits than in normal skin. Treatment of uncomplicated impetiginized pediatric AD with topical corticosteroids and cephalexin results in significant clinical improvement, even in subjects infected with MRSA. We propose that the inhibition of abnormal inflammation by the treatment regimen, resulting in the high levels of defensins, is involved in the improvement of AD and that systemic antibiotics do not appear to be necessary in secondary impetiginized AD.     

The Safety and Efficacy of Tacrolimus Ointment in Pediatric Patients with Atopic Dermatitis

Abstract: Atopic dermatitis (AD) is the most common skin disease in children, and its prevalence is increasing. It is a chronic disorder, characterized by intermittent flares and phases of remission. Treatment regimens often require multiple therapies. These can vary between patients, and in an individual patient, depending on the state of disease. The traditional treatment for AD flares is topical corticosteroids, which are fast acting and effective for relief of symptoms, but may cause adverse effects, including those resulting from systemic absorption, particularly in children. Topical calcineurin inhibitors (TCIs) are alternative treatments for AD. Tacrolimus ointment, a TCI, is approved for patients aged 2 years and older. Multiple studies have shown that tacrolimus is effective for short‐term relief of symptoms in pediatric patients with AD. Long‐term trials have demonstrated that the effectiveness of tacrolimus is maintained for up to 4 years in children. Additional studies have revealed that long‐term intermittent use of tacrolimus as part of maintenance therapy can prevent AD flares. Tacrolimus has a low potential for systemic accumulation, and analysis of long‐term studies indicates that it has a good safety profile. Treatment with tacrolimus, alone or in combination with topical corticosteroids for acute flares, may be a useful option for long‐term management of AD in pediatric patients.     

正确外用糖皮质激素

外用糖皮质激素是治疗很多皮肤病的主要方法之一,如果使用得当,安全有效,不良反应通常较小.如果患者把不同效力的外用糖皮质激素相混淆,过分地强调外用糖皮质激素的不良反应,并将其和系统应用糖皮质激素的不良反应等同起来,可造成临床上用药量不足,疗效不理想.英国皮肤病学专家就外用糖皮质激素的使用达成共识,结合该共识,介绍正确使用外用糖皮质激素的方法,消除对该类药物的恐惧感.     

S2k guideline for treatment of cutaneous lupus erythematosus – guided by the European Dermatology Forum (EDF) in cooperation with the European Academy of Dermatology and Venereology (EADV)

Cutaneous lupus erythematosus (CLE) is a rare inflammatory autoimmune disease with heterogeneous clinical manifestations. To date, no therapeutic agents have been licensed specifically for patients with this disease entity, and topical and systemic drugs are mostly used ‘off‐label’. The aim of the present guideline was to achieve a broad consensus on treatment strategies for patients with CLE by a European subcommittee, guided by the European Dermatology Forum (EDF) and supported by the European Academy of Dermatology and Venereology (EADV). In total, 16 European participants were included in this project and agreed on all recommendations. Topical corticosteroids remain the mainstay of treatment for localized CLE, and further topical agents, such as calcineurin inhibitors, are listed as alternative first‐line or second‐line topical therapeutic option. Antimalarials are recommended as first‐line and long‐term systemic treatment in all CLE patients with severe and/or widespread skin lesions, particularly in patients with a high risk of scarring and/or the development of systemic disease. In addition to antimalarials, systemic corticosteroids are recommended as first‐line treatment in highly active and/or severe CLE. Second‐ and third‐line systemic treatments include methotrexate, retinoids, dapsone and mycophenolate mofetil or mycophenolate acid, respectively. Thalidomide should only be used in selected therapy‐refractory CLE patients, preferably in addition to antimalarials. Several new therapeutic options, such as B‐cell‐ or interferon α‐targeted agents, need to be further evaluated in clinical trials to assess their efficacy and safety in the treatment of patients with CLE.     

Topical class I corticosteroids in 10 patients with bullous pemphigoid: correlation of the outcome with the severity degree of the disease and review of the literature

BACKGROUND: Treatment of bullous pemphigoid (BP) with systemic immunosuppressive agents, in particular with systemic corticosteroids, has many long-term side-effects. A dozen reports were published regarding the efficacy of topical corticosteroids in the treatment of bullous pemphigoid. OBJECTIVE: To evaluate the efficacy of potent class I topical corticosteroids in relation to the affected body surface area (BSA) in patients with bullous pemphigoid and to review the literature. METHODS: An open prospective trial with 10 patients with BP with measurement of the affected BSA. Treatment protocol consisted of three steps: potent class I topical corticosteroid treatment, systemic tetracyclines and systemic corticosteroids. Follow-up period was between 24 and 72 months. RESULTS: Our study suggests a correlation between the success rate of topical corticosteroid treatment and the body surface area initially affected: all patients with an affected BSA of less than 20% healed with topical treatment only. The patients with more than 40% affected BSA needed systemic treatment with steroids. CONCLUSION: Topical class I corticosteroids seem to be effective in healing lesions of BP, especially if less than 20% of the BSA is affected. This study comprises only 10 patients, making further studies necessary to draw definite conclusions.