Systemic therapy of atopic dermatitis

Atopic dermatitis is a chronic, relapsing, inflammatory skin disease. Topical therapy is the mainstay, but patients with widespread moderate to severe atopic dermatitis may require systemic therapy. Immunosuppressants, immune response modifiers, antihistamines and antibiotics are among the classes of systemic medications frequently used to treat extensive atopic dermatitis; the indications and scientific support for the use of these and other less commonly used medications will be reviewed in this article.     

Clinical remission of disseminated molluscum contagiosum infection in a patient with atopic dermatitis treated with dupilumab

Atopic dermatitis predisposes to skin infections, and on the other hand, some therapies used for atopic dermatitis may worsen viral infections whose lesions may be more diffuse and resistant to treatment. The authors present a patient with severe atopic dermatitis and disseminated molluscum contagiosum infection. The molluscum contagiosum did not clear with topical treatment, and it worsened her atopic dermatitis even more, so the authors started treatment with dupilumab. After two months, the patient's dermatitis went into clinical remission and there was resolution of the infection with no recurrence at the 12-month follow-up. Dupilumab is nowadays a promising treatment for severe atopic dermatitis. To our knowledge, only four reports of molluscum contagiosum during dupilumab therapy have been reported in the literature, with contrasting effects. According to the authors’ experience, treatment with dupilumab appears to be a safe alternative for patients with severe atopic dermatitis who are also infected with molluscum contagiosum, as opposed to other treatments such as systemic corticosteroids or cyclosporine.     

Long Term Treatment Concepts and Proactive Therapy for Atopic Eczema

Atopic eczema, also known as atopic dermatitis, is a frequent, highly pruritic, chronic skin disease, which is typically running in flares. The traditional treatment mainly consists of the reactive application of topical anti-inflammatory agents such as topical corticosteroids and topical calcineurin inhibitors. The short term benefit of this approach is well known, but long term remission between flares is difficult to achieve. Therefore, innovative long-term treatment strategies targeting flare prevention and skin barrier stabilization are needed. We and others have shown that normal looking, non-lesional skin of atopic dermatitis patients is immunobiologially not normal but characterized by an invisible inflammation and barrier defect. This has led to the novel concept of proactive therapy, which is defined as long-term, low-dose intermittent application of anti-inflammatory therapy to the previously affected skin, together with an ongoing emollient treatment of unaffected skin. This review article describes the most important long-term treatment options for atopic dermatitis, which includes emollient therapy, the novel concept of proactive treatment, the different ultraviolet light modalities and a selection of systemic immunosuppressive drugs and biologics. Current trial data, licensed indications, off-label use and relevant side effects of the different treatment modalities are summarized.     

Update “Systemic treatment of atopic dermatitis” of the S2k‐guideline on atopic dermatitis

This guideline is an update from August 2020 the S2k‐guideline “Atopic dermatitis” published in 2015. The reason for updating this chapter of the guideline were the current developments in the field of systemic therapy of atopic dermatitis. The agreed recommendations for systemic treatment in atopic dermatitis of the present guideline are based on current scientific data. Due to the approval of dupilumab for the treatment of moderate to severe atopic dermatitis, which cannot be treated sufficiently with topical drugs alone, this part of the guideline has now been adapted and newly consented. The indication for systemic therapy and the therapeutic response to topical and systemic treatment should be recorded and documented in a suitable form in clinic and practice. A standardized documentation of the indication for system therapy in atopic dermatitis can be recommended and is also part of the updated chapter of this guideline.     

Pimecrolimus

Pimecrolimus (Elidel) is a topically active, nonsteroid, calcineurin inhibitor that has shown efficacy in controlling symptoms of atopic dermatitis in adult and pediatric patients. Topical pimecrolimus 1% cream is approved in the US for the short-term and intermittent long-term treatment of mild-to-moderate atopic dermatitis in non-immunocompromised patients aged >/=2 years who do not respond well to, or may have adverse effects with, conventional treatments. Pimecrolimus 1% cream is an effective and well tolerated treatment for atopic dermatitis in infants, children, adolescents, and adults. Pimecrolimus is effective at reducing the incidence of disease flares and, thus, the need for rescue treatment with topical corticosteroids. The drug also improves the health-related quality of life (HR-QOL) of children and adolescents, and improves the QOL of parents of children with atopic dermatitis. Furthermore, pimecrolimus does not cause skin atrophy, a problem commonly associated with topical corticosteroids, and is not associated with clinically relevant systemic adverse events. Thus, topical pimecrolimus 1% cream is an effective treatment option for the management of mild-to-moderate atopic dermatitis.     

Future perspectives in the treatment of atopic dermatitis

Atopic dermatitis is a chronically relapsing inflammatory skin disease with an increasing prevalence. The guidelines for the treatment of atopic dermatitis enable us to manage many patients with atopic dermatitis under a global consensus, which also contributes to improving their quality of life. However, there remain some patients with atopic dermatitis whose symptoms cannot be satisfactorily controlled using the therapeutic management recommended by the guidelines. Recent genetic, immunological and physiological insights into the pathomechanisms of atopic dermatitis are expected to overcome the limitations of the currently available treatment. Advances in pharmacology and biotechnology will also provide more efficient and safer medications. In this review, the limitations of the currently available therapies and the advantages and disadvantages of new approaches for the treatment of atopic dermatitis including topical and systemic immunosuppressants as well as biologics and anti-pruritic agents are discussed. Potential new cellular targets for the treatment of atopic dermatitis are also illustrated.     

Vendajes húmedos: nuestra experiencia

A wide range of treatments are currently available for severe atopic dermatitis, including systemic therapies such as ciclosporin, corticosteroids, azathioprine, methotrexate, mofetil mycophenolate, and omalizumab. In patients who can no longer take systemic drugs or who need a dose reduction, wet-wrap treatment can be an excellent option.To date, wet wraps have mostly been used in severe cases of childhood atopic dermatitis. We report our experience with wet-wrap treatment in 5 adults with atopic dermatitis and 2 with nodular prurigo. The results were satisfactory and there were few adverse effects.     

Efficacy and Economics of Topical Calcineurin Inhibitors for the Treatment of Atopic Dermatitis

Atopic dermatitis is a chronic, relapsing inflammatory skin disease that frequently affects infants and children. The worldwide prevalence of atopic dermatitis is estimated to be 5-20% of the pediatric population. Studies have shown that atopic dermatitis is associated with considerable economic costs and decreased quality of life. There is no proven curative therapy at present for atopic dermatitis; first-line therapy has generally consisted of dry skin care, avoidance of triggers, application of topical corticosteroids, and administration of histamine H1 receptor antagonists (antihistamines) and oral antibacterials as appropriate. Topical corticosteroids, while effective in many patients, carry the concern of local and systemic adverse effects. As a result, physicians and patients are reluctant to utilize stronger topical corticosteroids in certain areas of the body and for prolonged periods of time. The purpose of this article is to review the efficacy and economics of topical calcineurin inhibitors in the treatment of atopic dermatitis. This new class of agents (specifically tacrolimus ointment and pimecrolimus cream) represents an exciting advance in the treatment of atopic dermatitis. Clinical data show that topical calcineurin inhibitors are effective and do not cause the adverse effects associated with topical corticosteroids. Several studies have provided evidence that topical calcineurin inhibitors positively affect the quality of life of patients and their caregivers. Compared with branded topical corticosteroids and previous standards of care, topical calcineurin inhibitors appear to be a cost-effective treatment option. Drawing comparisons between tacrolimus and pimecrolimus is difficult because definitive head-to-head comparative studies involving these drugs have not been conducted.     

Phototherapy for atopic eczema with narrow-band UVB

Management of atopic dermatitis has been less than satisfactory. Conventional therapy has not been particularly successful, and prolonged use of topical corticosteroids and systemic immunosuppressant drugs (eg, corticosteroids, cyclosporine, azathioprine) can result in severe cutaneous and systemic effects. We decided to evaluate the effect of UVB at 311 nm to treat 5 patients with moderate to severe atopic dermatitis. In each patient a mean cumulative dose of 9.2 J/cm² was applied over a mean of 19 irradiations. Narrow-band UVB notably reduced atopic dermatitis after 3 weeks in all patients. (J Am Acad Dermatol 1999;40:995-7.)     

Spotlight on Topical Pimecrolimus in Pediatric Atopic Dermatitis

Topical pimecrolimus 1% cream (Elidel®) [hereafter referred to as topical pimecrolimus] is a nonsteroidal alternative in the treatment of pediatric atopic dermatitis. In vehicle-controlled, short-term, continuous-use trials in pediatric patients with mild to moderate atopic dermatitis, topical pimecrolimus was effective in treating disease symptoms. Topical pimecrolimus was effective in preventing disease flares and reducing the need for topical corticosteroids in longer term, intermittent-use trials. In addition, topical pimecrolimus was associated with improvements in the health-related quality of life of pediatric patients with atopic dermatitis and their parents. In vehicle-controlled trials, topical pimecrolimus was generally as well tolerated as vehicle. Topical pimecrolimus showed similar efficacy to topical tacrolimus 0.03% ointment in a short-term, continuous-use trial and the two agents had a generally similar tolerability profile. Although comparative data between topical pimecrolimus and topical corticosteroids are lacking in pediatric patients, and the long-term tolerability (beyond 1–2 years) of topical pimecrolimus is yet to be established, topical pimecrolimus is a useful agent in the management of pediatric patients with mild to moderate atopic dermatitis who do not achieve satisfactory treatment with other topical pharmacologic treatments, including topical corticosteroids.     

Spotlight on topical pimecrolimus in atopic dermatitis

Pimecrolimus (SDZ ASM 981), an ascomycin derivative, is a nonsteroid, has anti-inflammatory activity, and has demonstrated efficacy in reducing symptoms of atopic dermatitis in adult and pediatric patients when applied topically. Compared with vehicle, topical pimecrolimus 1.0% cream was significantly more effective at reducing symptoms of atopic dermatitis, as measured by the Eczema Area and Severity Index (EASI), in infants aged 3 to 23 months, children aged 2 to 17 years, and adults. The median reductions from baseline in the total EASI score in adults after treatment with pimecrolimus 1.0% or corresponding vehicle twice daily for 3 weeks were 47 and 0%, respectively. In infants and children, treatment with pimecrolimus 1.0% twice daily for 6 weeks resulted in significant decreases in mean EASI scores compared with vehicle. The severity of pruritus was significantly reduced in patients of all age groups after topical treatment with pimecrolimus 1.0% cream. Compared with vehicle, the incidence of eczematous flares was also reduced by intermittent long-term use of topical pimecrolimus 1.0% in adults, children and infants. Sixty-one percent of children treated with pimecrolimus for 1 year completed the first 6 months of treatment without experiencing a flare, compared with 35% of patients who received vehicle. Furthermore, the use of topical corticosteroids for the treatment of uncontrolled flares in adults, children and infants was lower in the pimecrolimus groups than in the vehicle groups. Topical pimecrolimus 1.0% cream is well tolerated in atopic dermatitis patients of all age groups. There were no clinically relevant systemic adverse events reported from any of the studies in patients with atopic dermatitis. The most frequently reported adverse events pertained to application site reactions, such as burning and a feeling of warmth. In conclusion, topical pimecrolimus 1.0% cream has shown efficacy in the treatment of mild to moderate atopic dermatitis in infants, children and adults. Although tolerability data concerning infants and children have not yet been published in full, the drug appears to be well tolerated in all age groups, and there have been no reports of clinically relevant systemic adverse events. Furthermore, pimecrolimus has shown no potential for skin atrophy, a problem commonly associated with treatment with topical corticosteroids. Topical pimecrolimus 1.0% provides a promising and well tolerated treatment option in the management of infants, children and adults with mild to moderate atopic dermatitis.     

Recent developments in the treatment of adult atopic dermatitis

Atopic dermatitis is a common inflammatory skin condition with increasing incidence in recent decades. The mainstay of treatment has been the combination of emollients and topical corticosteroids, with the addition of systemic therapies in severe cases. New drugs such as the topical calcineurin inhibitors have shown promise in treating mild-to-severe atopic dermatitis. Other novel therapies that have been reported in the literature include leukotriene antagonists, monoclonal antibodies such as infliximab, leflunomide, recombinant interferon gamma and intravenous immunoglobulin. This review will focus on the treatment of adult atopic dermatitis.     

【开放获取】度普利尤单抗治疗特应性皮炎专家共识

【摘要】 特应性皮炎是一种常见的慢性炎症性皮肤病,以湿疹样皮疹和剧烈瘙痒为主要表现,可严重影响患者生活质量。中重度特应性皮炎往往需要系统治疗,传统的系统治疗对部分患者效果不佳或不能耐受。近年来,生物制剂开始用于临床治疗特应性皮炎,其中白细胞介素4受体拮抗剂度普利尤单抗已经在我国上市。中华医学会皮肤性病学分会特应性皮炎研究中心、中华医学会皮肤性病学分会儿童学组组织本领域部分专家讨论度普利尤单抗在中重度特应性皮炎治疗中的应用,并形成共识,希望本共识能为我国皮肤科医生临床应用度普利尤单抗治疗特应性皮炎提供参考。     

Severe atopic dermatitis and leflunomide: first clinical experience and highlights of pertinent experimental data

Atopic dermatitis is a common chronically relapsing disease affecting about 10 percent of children and 3 percent of adults. Currently, no standard management exists for long-term treatment. Topical corticosteroids and recently calcineurin-inhibitors are effective in most patients. In severe cases, however, systemic agents have to be employed. Their use may be limited by unwanted effects or insufficient long-term efficiency. Leflunomide is an immunomodulating and disease-modifying antirheumatic drug with anti-inflammatory and immunosuppressive activity, exhibiting an extremely long in vivo half life. Because T cells and eosinophils play an important role in the pathophysiology of atopic dermatitis, and long-term treatment is often required, leflunomide seems to be ideally suited for treatment of severe atopic eczema. We present a case highlighting the application regimen of leflunomide, and discuss the pathophysiological mechanism of action in atopic dermatitis. Because treatment benefit differs between patients, we propose the design of a proof-of-principle study for leflunomide in atopic dermatitis encompassing an evaluation of predictive markers for successful application.     

An open study of efficacy and safety of long-term treatment with mometasone furoate fatty cream in the treatment of adult patients with atopic dermatitis.

BACKGROUND: Atopic dermatitis is a severe chronic skin disease often deteriorated by the presence of microorganisms and often responds well to treatment with potent corticosteroids. However, the long-term use of potent topical corticosteroids are accompanied by side-effects such as skin atrophy. OBJECTIVE: To study the effect and safety of prophylactic treatment with mometasone furoate fatty cream (contains hexylene glycol) for 6 months in patients with atopic dermatitis. RESULTS: Sixty-one of 68 (90%) patients were still free of their disease after 6 months of twice weekly treatment and only one showed possible treatment related signs of skin atrophy. The number of Staphylococcus aureus and Pityrosporum ovale were significantly reduced in cleared patients. CONCLUSIONS: Mometasone furoate fatty cream is effective and safe both for treatment and as a prophylaxis in patients with atopic dermatitis.     

Omalizumab for the treatment of atopic dermatitis

Atopy is almost always associated with an elevated immunoglobulin (Ig) E production. Omalizumab is a monoclonal anti-IgE antibody that is currently indicated for the treatment of cases of asthma that satisfy certain criteria. A number of studies have been published on the usefulness of omalizumab in the treatment of atopic dermatitis, and the results have been variable. We present our experience in the treatment of 9 patients with severe atopic dermatitis refractory to at least 2 systemic drugs. All patients reported a decrease in pruritus and an improvement in quality of life. Good control of the skin disease was achieved with omalizumab in monotherapy in 2 patients, and there was a slight improvement in the eczematous lesions in 4 patients. Those patients who also had asthma achieved good control of their respiratory symptoms and did not require additional therapy. Omalizumab is a well-tolerated and safe drug that can be useful for the treatment of severe atopic dermatitis refractory to other systemic therapies. This monoclonal anti-IgE antibody is a major therapeutic advance as it opens the door to the management of atopic dermatitis using systemic immunomodulating therapies.     

Psychoneuroimmunology of psychological stress and atopic dermatitis: pathophysiologic and therapeutic updates

Atopic dermatitis is a chronic inflammatory skin disease characterized by impaired epidermal barrier function, inflammatory infiltration, extensive pruritus and a clinical course defined by symptomatic flares and remissions. The mechanisms of disease exacerbation are still poorly understood. Clinical occurrence of atopic dermatitis is often associated with psychological stress. In response to stress, upregulation of neuropeptide mediators in the brain, endocrine organs, and peripheral nervous system directly affect immune and resident cells in the skin. Lesional and non-lesional skin of patients with atopic dermatitis demonstrates increased mast cells and mast cell-nerve fiber contacts. In the setting of stress, sensory nerves release neuromediators that regulate inflammatory and immune responses, as well as barrier function. Progress towards elucidating these neuroimmune connections will refine our understanding of how emotional stress influences atopic dermatitis. Moreover, psychopharmacologic agents that modulate neuronal receptors or the amplification circuits of inflammation are attractive options for the treatment of not only atopic dermatitis, but also other stress-mediated inflammatory skin diseases.     

Validation of the Eczema Area and Severity Index for atopic dermatitis in a cohort of 1550 patients from the pimecrolimus cream 1% randomized controlled clinical trials programme

OBJECTIVE: To validate the Eczema Area and Severity Index (EASI) by assessing its internal consistency, reliability and sensitivity to change and by correlating it to other efficacy parameters. DESIGN: Three short-term and two long-term double-blind, randomized, controlled trials, performed in 138 study centres in Europe, South Africa, Australia, New Zealand, and North and South America. PATIENTS AND METHODS: In total, 1550 paediatric patients with atopic dermatitis were studied. Pimecrolimus cream 1% was used twice daily to treat atopic dermatitis. The three short-term studies were placebo controlled. The two long-term studies evaluated the efficacy and safety of early intervention with pimecrolimus to prevent progression to disease flare requiring topical corticosteroid treatment, compared with reactive treatment with topical corticosteroids to treat flares of atopic dermatitis. MAIN OUTCOME MEASURES: Five parameters were measured: (i) the EASI (range of score 0-72); (ii) Investigators' Global Assessment (IGA), using a six-point (0-5) scale; (iii) patients' assessment, using a four-point (0-3) scale; (iv) severity of pruritus assessment, using a four-point (0-3) scale; and (v) a quality-of-life evaluation. RESULTS: The EASI score varied in parallel and in correlation with the IGA, pruritus and patients' assessment. All correlation coefficients were statistically different from 0 (P < 0.05). The EASI correlated well with each of its components, and all paired comparisons were within agreed limits. The EASI showed good sensitivity to changes in severity. CONCLUSION: In a large, multinational patient population with atopic dermatitis, the EASI showed good validity, reliability and sensitivity to change and correlated well with other measures of severity. It therefore qualifies as a valid method of assessment in clinical studies of atopic dermatitis.     

Psoriasis in infancy: therapy with calcipotriene ointment.

Psoriasis in infancy is often more therapeutically challenging than atopic and seborrheic dermatitis. The generalized nature of psoriasis and the intensity of inflammation often reduce the efficacy of topical corticosteroids. Furthermore, involvement of intertriginous skin and the presence of scalp disease limit the potency of the topical steroids that can be prescribed. We report on an infant treated with topical calcipotriene for infantile psoriasis who experienced greater benefit than he had with standard corticosteroid medications. Laboratory testing for calcium metabolism was normal during the course of therapy. We conclude that calcipotriene can be a safe and effective therapy for psoriasis in early infancy.