Principles of topical treatment

Abnormalities of the skin in children are very common. Any paediatric dermatology clinic would include children with ichthyoses, napkin rashes, various naevi, psoriasis, and a number of infections such as impetigo, scabies, warts, molluscum contagiosum and herpes simplex. However, the most frequent and troublesome problem would be the ‘eczemas’, particularly ‘infantile eczema’, ‘eczema’, ‘atopic eczema’ or, as I shall call it, ‘atopic dermatitis’ (AD). I suspect that AD is the skin disorder with which most paediatricians have most trouble, and so have concentrated on this.     

Cytokine dermatitis and febrile seizure from imiquimod

Cytokine dermatitis is a well-known and common clinical adverse effect of imiquimod 5% cream (Aldara, 3M). Data from initial Phase III clinical trials reveal a minority of study drug patients experience systemic adverse effects, including fever, arthralgia, headache, myalgia, and lymphadenopathy. These adverse effects are caused, presumably, from increased absorption of study drug over the area of dermatitis, leading to systemic cytokine release. Furthermore, the incidence of systemic reactions was rarely statistically increased above control patients. We describe herein a case of severe cytokine dermatitis in a 2-year-old female patient treated with daily imiquimod for molluscum contagiosum who subsequently developed febrile seizure. We believe this to be the first reported case of seizure associated with imiquimod 5% cream (Aldara, 3M) in a pediatric setting.     

Unmet medical needs in the treatment of atopic dermatitis in infants: An Expert consensus on safety and efficacy of pimecrolimus

Atopic dermatitis (AD) is a common skin disease during infancy, which imposes a considerable burden on patients, their families, and the society, requiring effective treatment options that result in rapid and sustained symptom relief. Additionally, early treatment may prevent the development of atopic comorbidities by restoring the skin barrier. Currently, topical standard-of-care for AD in infants includes emollients and topical corticosteroids (TCS) to treat and reduce the risk of flares. However, only few have been approved for infants and long-term maintenance therapy with TCS is not indicated due to potential local and systemic side effects, including skin atrophy. Accordingly, the recently updated European guidelines for treatment of AD recommend topical calcineurin inhibitors (TCIs) for long-term use, treatment of sensitive skin areas, and for use in the pediatric population. Evidence on the use of TCIs for infants has almost been exclusively collected for pimecrolimus, with >4000 infants evaluated in clinical trials, consistently confirming that pimecrolimus is a safe and effective treatment for infants with AD. Nevertheless, its use is still restricted in most countries to children above the age of 2 years due to initial and mostly theoretical safety concerns. Based on a careful review of the available evidence of clinical trials, post-marketing surveillance, and epidemiological studies, an Expert Panel of European dermatologists and pediatric allergologists concluded that these safety concerns are no longer valid. Therefore, pimecrolimus offers a safe and effective alternative to TCS in infants aged 3 months and above, and labeling restrictions in this age group are no longer justified.     

Tacrolimus ointment does not affect the immediate response to vaccination, the generation of immune memory, or humoral and cell-mediated immunity in children

Background

Concern exists that the prolonged application of immunomodulators to treat atopic dermatitis may cause systemic immunosuppression.

Aims

In a 7‐month, multicentre, randomised, controlled trial, we investigated the equivalence of response to vaccination against meningococcal serogroup C disease with a protein‐conjugate vaccine in children (2–11 years) with moderate to severe atopic dermatitis, by applying either 0.03% tacrolimus ointment (TAC‐O; n = 21) or a hydrocortisone ointment regimen (HC‐O; n = 111).

Methods

TAC‐O was applied twice daily (bid) for 3 weeks, and thereafter daily until clearance. 1% hydrocortisone acetate (HA) for head/neck and 0.1% hydrocortisone butyrate ointment for trunk/limbs was applied bid for 2 weeks; thereafter HA was applied bid to all affected areas. At week 1, patients were vaccinated with protein‐conjugate vaccine against meningococcal serogroup C, and challenged at month 6 with low dose meningococcal polysaccharide vaccine. The control group (44 non‐atopic dermatatits children) received the primary vaccination and challenge dose. Assessments were made at baseline, weeks 1 and 5, and months 6 and 7. The primary end point was the percentage of patients with a serum bactericidal antibody (SBA) titre ⩾8 at the week 5 visit.

Results

The response rate (patients with SBA titre ⩾8) was 97.5% (confidence interval (CI) approximately 97.3 to 100), 99.1% (94.8 to 100) and 97.7% (93.3 to 100) in the TAC‐O, HC‐O and control groups, respectively.

Conclusions

The immune response to vaccination against meningococcal serogroup C in children with atopic dermatitis applying either 0.03% TAC‐O or HC is equivalent. Ointment application does not affect the immediate response to vaccination, generation of immune memory or humoral and cell‐mediated immunity.Atopic dermatitis is a chronic, pruritic, inflammatory skin disease that can seriously affect the health and quality of life of the patient. Intense itching is the predominant symptom and excessive scratching can cause damaging excoriations, erosions and lichenification of the skin.¹ The disease is most common during childhood, with 80–90% of children having onset before 5 years of age,² and is likely to persist into adulthood in those who are severely affected.³ The exact pathogenesis of atopic dermatitis is unknown, but it is recognised that T cell‐mediated reactions⁴ and increased eosinophil levels⁵ are involved in the inflammatory response.Atopic dermatitis usually has a relapsing course, and requires long‐term continuous or intermittent treatment. Emollients provide symptomatic relief by reducing the intense itching and inflammation. However, for the treatment of acute exacerbations, most patients require topical treatment with either corticosteroids or calcineurin inhibitors such as tacrolimus or pimecrolimus. Children with moderate to severe atopic dermatitis have large affected body surface areas, often with open and weeping lesions, and this raises concerns that the prolonged application of topical immunomodulators may cause systemic immunosuppression. Current evidence is that the percutaneous absorption of tacrolimus and pimecrolimus is minimal.^6,7,8,9 Nonetheless, as atopic dermatitis often occurs in young children who are undergoing childhood immunisation programmes, it is important to determine whether topical immunomodulators have an effect on the humoral and cell‐mediated immune response to vaccination.Information about the immune response to vaccination of patients with atopic dermatitis treated with topical immunomodulators is scarce. Several studies, however, have investigated the immune response to vaccination of children with corticosteroid‐dependent asthma. It seems that children receiving short‐term low to moderate daily maintenance doses of systemic corticosteroids can receive live virus vaccines without marked suppression of the antibody response.¹⁰ Hanania et al¹¹ found that children with asthma receiving high‐dose inhaled corticosteroids had a normal response to A antigens of the inactivated influenza vaccine. Other studies on children with asthma found no association between inhaled corticosteroid use and varicella vaccine failure,¹² or an impaired immune response to pneumococcal vaccines.¹³ With regard to children with atopic dermatitis applying topical immunomodulators, Papp et al¹⁴ reported that treating children with 1% pimecrolimus cream for up to 2 years did not affect the seropositivity rates for tetanus, diphtheria, measles or rubella after vaccination. In a small US study of 23 children with atopic dermatitis, the application of 0.03% tacrolimus ointment (TAC‐O) for 7 weeks had no effect on the serological response to pneumococcal polysaccharide vaccine.¹⁵To increase our knowledge of the immune response to vaccination of children with atopic dermatitis treated with topical immunomodulators, we investigated whether the application of a hydrocortisone regimen or 0.03% TAC‐O had any effect on the immune response after vaccination against meningococcal serogroup C disease.     

Interferon-alpha treatment of molluscum contagiosum in a patient with hyperimmunoglobulin E syndrome

We report widely disseminated molluscum contagiosum that occurred in a 9-year-old boy secondary to hyperimmunoglobulin E syndrome, a primary immunodeficiency disorder. Cutaneous examination revealed numerous, widespread, skin-colored to translucent, firm, umbilicated papules of varying sizes. They were distributed throughout the perineal and gluteal areas and bilaterally over his lower limbs. A biopsy specimen from his skin lesion demonstrated lobulated epidermal growth that consisted of keratinocytes with large intracytoplasmic eosinophilic inclusion bodies and a central crater. These findings were consistent with the diagnosis of molluscum contagiosum. Many treatments for his skin lesions were ineffective, including physical destruction or manual extrusion of the lesions; cryotherapy; curettage; and topical therapies with phenol, trichloroacetic acid, and imiquimod. The patient was treated successfully with subcutaneous interferon-alpha for 6 months without any adverse effect.     

Mechanistic insights into topical tacrolimus for the treatment of atopic dermatitis

More than 15 years have passed since the clinical launch of topical tacrolimus for the treatment of atopic dermatitis. Its efficacy and safety have been clearly demonstrated in many global and domestic short‐term and long‐term clinical trials. Although the prolonged external application of steroids causes many adverse reactions including cutaneous atrophy, no such reactions occur with the use of topical tacrolimus. Therefore, the therapeutic guidelines recommend a combined topical treatment with tacrolimus and steroids. Tacrolimus is a potent immunosuppressant. However, recent studies have revealed its diverse action on the cardinal pathomechanisms of atopic dermatitis. In this review, we summarize the mechanistic role of tacrolimus in various aspects of allergic inflammation including mast cell activation, innate allergic response, pruritus, sensory nerve activation, and skin barrier dysfunction.     

Advances in pediatric asthma and atopic dermatitis

PURPOSE OF REVIEW: Allergic diseases, including asthma, allergic rhinitis, atopic dermatitis, food allergy, and urticaria are common in general pediatric practice. This review highlights several significant advances in pediatric allergy over the past year, focusing on asthma and atopic dermatitis. RECENT FINDINGS: With increasing options for the treatment of allergic diseases, much work is now focused on methods for individualizing treatments to a patient's phenotype and genotype. Progress over the past year includes the characterization of effects of regular albuterol use in patients with genetic variations in the beta-adrenergic receptor. Maintenance asthma regimens for children in the first years of life are also an ongoing focus. The relation between upper airway allergic inflammation and asthma has continued to accumulate support and now extends to the middle ear. Environmental influences on asthma and interventions have been described, including environmental controls for asthma and the role of air pollution on lung development in children. Finally, concerns have been raised regarding the use of topical immunomodulators in young children with atopic dermatitis. SUMMARY: Progress continues in the care of children with atopic diseases. Attention to treatment with appropriate medications, patient-individualized environmental controls, and extensive education are the keys to successfully treating atopic children. This review highlights several recent advances but is not intended to be a comprehensive review.     

Pimecrolimus in atopic dermatitis: Consensus on safety and the need to allow use in infants

Atopic dermatitis (AD) is a distressing dermatological disease, which is highly prevalent during infancy, can persist into later life and requires long‐term management with anti‐inflammatory compounds. The introduction of the topical calcineurin inhibitors (TCIs), tacrolimus and pimecrolimus, more than 10 yr ago was a major breakthrough for the topical anti‐inflammatory treatment of AD. Pimecrolimus 1% is approved for second‐line use in children (≥2 yr old) and adults with mild‐to‐moderate AD. The age restriction was emphasized in a boxed warning added by the FDA in January 2006, which also highlights the lack of long‐term safety data and the theoretical risk of skin malignancy and lymphoma. Since then, pimecrolimus has been extensively investigated in short‐ and long‐term studies including over 4000 infants (<2 yr old). These studies showed that pimecrolimus effectively treats AD in infants, with sustained improvement with long‐term intermittent use. Unlike topical corticosteroids, long‐term TCI use does not carry the risks of skin atrophy, impaired epidermal barrier function or enhanced percutaneous absorption, and so is suitable for AD treatment especially in sensitive skin areas. Most importantly, the studies of pimecrolimus in infants provided no evidence for systemic immunosuppression, and a comprehensive body of evidence from clinical studies, post‐marketing surveillance and epidemiological investigations does not support potential safety concerns. In conclusion, the authors consider that the labelling restrictions regarding the use of pimecrolimus in infants are no longer justified and recommend that the validity of the boxed warning for TCIs should be reconsidered.     

Effectiveness of imiquimod 5% cream for treatment of extensive anogenital warts in a seven-year-old child

Conventional treatment options for anogenital warts in prepubertal children rely on chemical and physical destruction methods that can be difficult and painful and frequently require the use of general anesthesia. Other approaches include the use of immunotherapies, as topical imiquimod and intralesional or systemic interferon. We report a 7-year-old girl with extensive anogenital warts who was successfully treated with topical 5% imiquimod cream.     

How and when to treat molluscum contagiosum and warts in children

Warts and molluscum contagiosum are common skin diseases in children and are usually self-limiting. The decision of whether to treat children with molluscum or warts should be individualized to the patient and his or her family. Considerations include how symptomatic the lesions are, the extent and duration of disease, the ability of the child and the parents to tolerate and comply with treatment recommendations, and any underlying medical conditions (Table, see page 219). Recurrences of molluscum contagiosum and especially warts are common, and realistic expectations regarding the potential for treatment failure and recurrence should be discussed with the child and his or her family prior to initiating any therapy. As pediatric practitioners, we all remain acutely aware of our patients' physical and psychological development and the potential for any intervention to influence this development. Although various treatment modalities now exist for the treatment of these viral diseases, any intervention should be balanced against these considerations.     

中国儿童超说明书用药管理现状及认知度的横断面调查

目的：调查中国儿童超说明书用药的管理现状及医务人员的认知度,为规范儿童超说明书用药提供依据。方法：以横断面研究设计,在中国大陆每个省至少选择一家具备儿科资质的医疗单位;调查人群：儿科医生、药师、护士和医务科行政人员;由儿科临床专家、药学专家、流行病学专家和药事管理专家组成的工作小组自制《中国儿童超说明书用药调查表》,包括基本信息维度6个条目,所在医院超说明书用药的现状及管理维度11个条目,超说明书用药及其管理的认知和《中国儿科超说明书用药专家共识》知晓情况维度33个条目,行网络问卷调查。结果：全国31省436家医院参与调查,其中儿童专科医院36家,妇幼保健院50家,综合性医院350家;一级医院20家,二级医院185家,三级医院231家。收集到有效问卷2116份,其中医生621名、药师755名、护士531名和医务科行政人员209名;初级职称712名、中级职称894名、高级职称510名。63.8%的医生有开具超说明书用药处方经历,职称越高,超说明书用药的现象越多;18.8%的医生经常超说明书用药,职称越高经常超说明书用药发生概率越大;19.4%的医生超说明书用药时都没有得到药师或护士提醒。药师发现过医生超说明书用药的情况是普遍存在的,不论药师职称的高与低（87.1%~98.3%）,不论医院级别（82.1%~94.2%）,6.9%~8.8%的护士面对医生超说明书用药拒绝执行医嘱。60.6%的被调查医院针对超说明书用药有统一制度流程,其中三级医院的比例高于一、二级医院,儿童专科医院的比例高于综合医院和妇幼保健院。70%的被调查者认为超说明书用药并不违法,但是80%以上的被调查者肯定超说明书用药存在风险。在医生、药师、护士和医务科行政人员中,2016年中华医学会儿科学分会临床药理学组提出的《中国儿科超说明书用药专家共识》知晓率分别为51.2%、56.8%、35.8%和45.4%。结论：中国大陆儿童超说明书用药现象普遍存在,急需统一有效的管理模式,需要制定出适合中国大陆的超说明书用药流程,加强医务人员培训,推进儿童规范化超说明书用药。     

Management of atopic dermatitis in the pediatric population

Atopic dermatitis, one of the most common skin disorders in young children, has a prevalence of 10% to 20% in the first decade of life. It is a chronic illness that requires a multifaceted treatment strategy in the setting of limited therapeutic options. Balancing safety concerns with efficacious treatment is of particular importance in the pediatric population. Parents of patients with atopic dermatitis turn to their primary caregivers for guidance regarding this physically demanding and psychologically stressful condition. In addition to serving as a review of atopic dermatitis, this article delves into the state-of-the-art therapeutic options and includes a detailed review of the differences between topical corticosteroids and topical calcineurin inhibitors. We also discuss new treatment strategies that are being used by atopic dermatitis specialists, such as comprehensive "education-as-intervention" models, wet wraps, bleach baths, and systemic immunomodulatory therapies.     

Recognizing and managing eczematous id reactions to molluscum contagiosum virus in children

Molluscum contagiosum (MC) is a self-limiting cutaneous viral eruption that is very common in children. MC infection can trigger an eczematous reaction around molluscum papules known as a hypersensitivity or an id reaction. In addition, a hypersensitivity reaction can occasionally occur at sites distant from the primary molluscum papules. These eczematous reactions are often asymptomatic or minimally pruritic. We believe that id reactions represent an immunologically mediated host response to MC virus and a harbinger of regression. Therefore, these reactions often do not require treatment other than emollients. Moreover, topical steroids or immunomodulators may suppress this process and potentiate the spread of the primary MC infection. However, in symptomatic patients, treatment should not be withheld and short-course treatments of topical corticosteroids may be used. In this case series, we describe 3 cases of hypersensitivity reactions in otherwise healthy children with MC. We hope that our report will make clinicians more aware of this common eczematous response to MC and will improve the management and counseling of these patients and their parents.     

Food allergy and atopic dermatitis in infancy: an epidemiologic study

Atopic dermatitis is common in infancy. The role of food allergy in atopic dermatitis of infancy is unclear. We examined the relationship between atopic dermatitis and immunoglobulin E (IgE)-mediated food allergy in infancy. A birth cohort of 620 infants with a family history of eczema, asthma, hayfever or immediate food allergy in a parent or sibling: 487 children had complete data including skin prick tests (SPTs) to evaluate IgE-mediated food allergy to cow milk, egg and peanut. Participants were grouped as no atopic dermatitis (Gp 0) or in quartiles of increasing severity of atopic dermatitis (Gps 1-4) quantified by days of topical steroid use as reported monthly. Adverse reactions to foods were recorded. The cumulative prevalence of atopic dermatitis was 28.9% to 12 months (10.3% of the cohort of moderate severity). As atopic dermatitis severity increased so did the prevalence of IgE-mediated food allergy (Gp 0, 40/346 vs. Gp 1, 6/36 vs. Gp 2, 8/35 vs. Gp 3, 12/35 vs. Gp 4, 24/35; chi(2) = 76; p < 10(-6)), and the frequency of reported adverse food allergy reactions (Gp 0, 43/346 vs. Gp 1, 4/36 vs. Gp 2, 8/35, vs. Gp 3, 5/35, vs. Gp 4, 13/35; chi(2) = 17; p = 0.002). The relative risk of an infant with atopic dermatitis having IgE-mediated food allergy is 5.9 for the most severely affected group. Atopic dermatitis is common in infancy. There is a strong association between IgE-mediated food allergy and atopic dermatitis in this age group.     

Management of tacrolimus‐associated food allergy after liver transplantation

Increasingly, food allergy associated with tacrolimus after pediatric living‐donor liver transplantation (LT) has been reported. Tacrolimus prevents the activation of T cells by blocking calcineurin, thus producing an immunosuppressive effect, but tacrolimus induces an imbalance in T‐helper type 1 (Th1) and Th2 cells in the food allergy process. This report describes a case of tacrolimus‐associated food allergy after pediatric living‐donor LT. The patient was a 7‐year‐old Japanese girl who had undergone living‐donor LT at 12 months of age, and whom we first saw in the clinic at age 18 months. She received immunosuppressive therapy by tacrolimus after transplantation. Atopic dermatitis developed in post‐transplant month 18. Stridor, facial edema, lip swelling, and skin erythema after consuming tempura udon containing wheat occurred in post‐transplant month 39, and she was subsequently diagnosed with anaphylactic shock. Eosinophilic leukocyte and serum immunoglobulin (Ig)E increased, and specific IgE was positive for some food allergens. Pharmacotherapy was therefore changed from tacrolimus to cyclosporine A, after which eosinophilic leukocyte and serum IgE decreased and atopic dermatitis improved.     

Atopic dermatitis. A review of diagnosis, pathogenesis, and management

Atopic dermatitis, one of the common dermatologic abnormalities encountered by pediatricians in clinical practice, is a chronic pruritic skin disorder occurring in individuals with a personal or family history of atopic disease such as asthma or allergic rhinitis. Atopic dermatitis appears to be an inherited disease, although the mode of inheritance has not been established. Clinically, its course can be divided into stages: infantile, childhood, and adult. Recognition of atopic dermatitis in any of these stages should facilitate appropriate treatment. This general overview examines several aspects of the disease, including current concepts of clinical manifestations, differential diagnosis, pathogenesis, and treatment.     

Atopic diseases of childhood

PURPOSE OF REVIEW: The incidence of atopic diseases, including atopic dermatitis, allergic rhinitis, and asthma, has increased in developed countries over the past several decades. These diseases comprise a large component of general pediatric practice. This review will highlight some of the recent advances in understanding the pathogenesis and natural history of these diseases, as well as the current approaches to the treatment of children with atopic diseases. RECENT FINDINGS: Recent studies have identified multiple risk factors for the development and progression of atopic diseases. As a result, much research is focused on identifying therapies that can be initiated at a young age to prevent disease progression. New treatment options have become available in recent years, such as topical immunomodulators for atopic dermatitis, leukotriene antagonists for seasonal allergic rhinitis, and alpha-immunoglobulin E therapy for asthma. The importance of viewing allergic rhinitis and asthma as disorders of a single airway has been emphasized. Finally, an update on the national asthma guidelines was recently released in an effort to promote optimal asthma care. SUMMARY: This review summarizes many of the recent advances in the diagnosis and treatment of atopic diseases in children. Although not intended to be a comprehensive review of this broad field, it provides a framework for appreciating the complexity of these diseases and for effectively managing them.     

The association of atopic dermatitis in infancy with immunoglobulin E food sensitization

OBJECTIVE: To prospectively investigate the association of high levels of immunoglobulin E (IgE) sensitization to foods and the presence of atopic dermatitis (judged by reported topical steroid use during the first 16 months of life) in a birth cohort of 620 Australian children "at risk" of allergic disease because of family history. RESULTS: A total of 559 of the children in the cohort were fully evaluated, and the cumulative prevalence of atopic dermatitis was 24%. More children in the cohort who had atopic dermatitis had strongly positive skin test results (> or = 4+, histamine equivalent units, > or = approximately 6-mm wheal), consistent with IgE food sensitization to either cow's milk, egg, or peanut at 6 months (22% vs 5%, chi(2) = 35; P < 10(-6)) and at 12 months (36% vs 11%, chi(2) = 41; P < 10(-6)) than those without atopic dermatitis. The calculated attributable risk percent for IgE food sensitization as a cause of atopic dermatitis was 65% and 64% at these times. In a separate group of infants with severe atopic dermatitis, the equivalent rates of IgE food sensitization at 6 months was 83% and at 12 months, 65%. CONCLUSION: IgE food sensitization is a major risk factor for the presence of atopic dermatitis in infancy.     

Pattern of Pediatric Dermatoses at a Referral Centre

Objective

To determine the pattern of skin disorders seen among children attending a Medical College Hospital, Bangalore

Methods

All children 18 y and below attending the Pediatric Dermatology OPD with skin diseases between the period of January 2011 and June 2011 were included in the study.

Results

A total of 1,090 new cases (boys 589; girls 501) with 1,118 dermatoses were recorded during this period. Twenty eight children had more than one dermatoses. Most of the disorders were seen between 5 and 11 y age group. The most common dermatoses was infections and infestations (32.47 %) followed by eczematous eruptions and dermatitis (20.66 %), papulosquamous and related disorders (6.08 %) and pigmentary disorders (5.81 %). Insect bite reactions and papular urticaria formed 5.1 %. Acne was seen in 5.28 % of children followed by urticaria (3.67 %), photodermatoses 2.5 % and genetic disorders (3.04 %).

Conclusions

In the present setting bacterial infections and scabies still remained the most common pediatric dermatoses followed by molluscum contagiosum and atopic dermatitis. Childhood psoriasis contributed to major part of the study among papulosquamous disorders.