Atopic dermatitis is a chronic inflammatory skin disease that disrupts the daily work and social lives of patients. Treatment of atopic dermatitis makes use of a variety of therapies, from medications to nutritional supplements to psychotherapy. Health outcomes research evaluates the efficacy, safety, and impact on health-related quality of life of these therapies.
Atopic dermatitis or eczema is a chronic inflammatory skin disease characterized by itchy, scaly lesions. The Hanifin and Rajka criteria require that three or more major criteria and three or more minor criteria be present for diagnosis ( Box 1 ). Major criteria include pruritus, a typical morphology and distribution, a chronic relapsing dermatitis, and a personal or family history of atopy. Examples of minor criteria include xerosis, raised serum IgE, and an early age of onset.
Major Criteria
Pruritus, a typical morphology and distribution, a chronic relapsing dermatitis, and a personal or family history of atopy
Minor Criteria
Xerosis; ichthyosis, palmar hyperlinearity, or keratosis pilaris; immediate (type 1) skin-test reactivity; elevated serum IgE; early age of onset; tendency toward cutaneous infections (especially Staphylococcus aureus and herpes simplex) or impaired cell-mediated immunity; tendency toward nonspecific hand or foot dermatitis; nipple eczema; cheilitis; recurrent conjunctivitis; Dennie-Morgan infraorbital fold; keratoconus; anterior subcapsular cataracts; orbital darkening; facial pallor or facial erythema; pityriasis alba; anterior neck folds; itch when sweating; intolerance to wool and lipid solvents; perifollicular accentuation; food intolerance; course influenced by environmental or emotional factors; white dermographism or delayed blanch
Prevalence and incidence of atopic dermatitis
Atopic dermatitis is a common skin disease that affects up to 25% of children worldwide. The condition begins in infancy in 60% of cases. Data from the 2003 National Survey of Children’s Health estimated an overall prevalence rate of 10.7% for atopic dermatitis in children younger than 17 years in the United States, with a range from 8.7% to 18.1%.
Assessment of health outcomes in atopic dermatitis
Although primarily focused on disease severity and quality of life, the range of potential measurable health outcomes in atopic dermatitis is wide. Disease-severity measurements can include objective clinical parameters that assess degree of erythema, exudation, and excoriations; they can also include subjective criteria such as itching and sleep disturbance. Quality of life is defined as the perception of disease impact on physical, psychological, and social well-being.
Disease-severity scales in atopic dermatitis include disease-specific and non–disease-specific scales. Examples of disease-specific scales include the Severity Scoring of Atopic Dermatitis (SCORAD), Eczema Area and Severity Index (EASI), and Six Area, Six Sign Atopic Dermatitis (SASSAD), while non–disease-specific scales include the Investigators’ Global Assessment (IGA), Total Body Severity Assessment (TBSA), and Visual Analog Scale (VAS). Since the number and type of assessed clinical features vary between scales, a lack of standardization of objective severity scales exists for atopic dermatitis. With some scales assessing multiple body sites while other scales assess only the most severely affected site, diversity exists in the methods of measuring disease extent. Disease-severity scales commonly used in randomized controlled trials (RCTs) of atopic dermatitis treatment include SCORAD, EASI, and IGA. The characteristic features, validity, and reliability of these scales are discussed in the following section.
The SCORAD was developed in 1993 by the European Task Force on Atopic Dermatitis. This scale uses the “rule of nines” to assess disease extent and evaluates 5 clinical characteristics to determine disease severity: (1) erythema, (2) edema/papulation, (3) oozing/crusts, (4) excoriation, and (5) lichenification. The SCORAD also assesses subjective symptoms of pruritus and sleep loss with VAS. Extent of disease, disease severity, and subjective symptoms combine to give a maximum possible score of 103. Although it is a combined score, the three aspects can be separated and used individually if necessary. Of all the severity scales used in atopic dermatitis, the SCORAD is the most widely validated disease-severity instrument. The SCORAD is valid and reliable and has shown excellent agreement with global assessments of disease severity. However, some studies have shown interobserver variation in scoring lichenification and extent of disease.
The EASI was developed by modifying the PASI (Psoriasis Area and Severity Index), a widely accepted and standardized scoring system for psoriasis. The EASI assesses extent of disease at four body sites and measures four clinical signs on a scale of 0 to 3: (1) erythema, (2) induration/papulation, (3) excoriation, and (4) lichenification. The EASI confers a maximum score of 72 and evaluates two dimensions of atopic dermatitis: disease extent and clinical signs. Although some investigators contend that subjective symptoms may be the most important marker for assessing patient morbidity and may act as a good indicator for disease severity, unlike the SCORAD, the EASI does not assess symptoms such as pruritus and sleep loss. In a large validation study with a cohort of 1550 pediatric patients, the EASI was found to have excellent validity, internal consistency, and sensitivity to change. While the EASI is a valid and reliable instrument, most interobserver variability lies in the dimension of induration/papulation.
The IGA allows investigators to assess overall disease severity at one given time point, and it consists of a 6-point severity scale from “clear” to “very severe” disease (0 = clear, 1 = almost clear, 2 = mild disease, 3 = moderate disease, 4 = severe disease, and 5 = very severe disease). The IGA uses clinical characteristics of erythema, infiltration, papulation, oozing, and crusting as guidelines for the overall severity assessment. To the authors’ knowledge, the IGA has not been validated as an outcome measure. However, the IGA has been used to validate other outcome scales. Potential weaknesses of the IGA include lack of responsiveness and discrimination for disease severity and lack of subjective symptoms.
Quality-of-life scales also include both disease-specific and non–disease-specific scales. Instruments specific to atopic dermatitis include the Dermatitis Family Impact (DFI), Parent’s Index of Quality of Life in Atopic Dermatitis (PIQoL-AD), and Quality of Life Index for Atopic Dermatitis (QoLIAD). Non–disease-specific scales include the Dermatology Life Quality Index (DLQI), Children’s Dermatology Life Quality Index (CDLQI), and Infants’ Dermatitis Quality of Life Index (IDQOL). Quality-of-life measurements are increasingly being recognized as important outcome measures but currently are primarily used to supplement existing measurement tools in dermatology. Quality-of-life scales commonly used in RCTs of the treatment of atopic dermatitis are the CDLQI, DFI, and DLQI. The features and validity of these scales are reviewed in the following section.
The CDLQI, which purposes to measure the quality of life in children with skin disease, was developed by Lewis-Jones and Finlay and validated in 1995. The questionnaire was designed for children of ages 4 through 16 years. The CDLQI is completed by the child with assistance from an adult if necessary. The survey consists of 10 questions that evaluate the aspects of a child’s life that could be affected by their skin disease. The instrument includes physical symptoms such as itching and sleep loss and psychosocial questions regarding friendships, bullying, school performance, sports participation, and enjoyment of vacation. The questions are individually graded from 0 to 3 with a maximum possible combined score of 30; the higher scores represent worse quality of life. In the initial validation study, children with atopic eczema accounted for 20% of all patients. To determine test-retest repeatability, the CDLQI was used in a population of children without skin disease.
Since its validation, the CDLQI has been used in numerous studies to determine the effectiveness of interventions in children with atopic dermatitis. The CDLQI has been translated and validated in Cantonese. A cartoon version of the CDLQI, which appears to be quicker and preferred by children, was validated in 2003.
The DFI questionnaire was developed in 1998 by Lawson, Lewis-Jones, Finlay, Reid, and Owens to help measure how family life is affected by a child suffering from atopic dermatitis. The DFI is designed to be completed by a caretaker of the child, who is often the parent. It consists of 10 questions related to housework, food preparation and feeding, sleep, family leisure activity, shopping, fatigue, emotional distress, and relationships. Each question is graded from 0 to 3 with a maximum combined score of 30. The DFI was deemed valid, reliable, and sensitive to change in multiple studies. Two of the studies assessing validity of the instrument used the separate components of the DFI instead of the total score as was originally intended. The DFI has also been validated in Malay and Portuguese.
The DLQI was developed in 1994 by Finlay and Khan to measure quality of life in adults older than 18 years in routine clinical-practice settings. The DLQI is a 10-item questionnaire that evaluates skin symptoms, feelings of embarrassment, and how skin disease has affected day-to-day activities, working life, and social life. Similar to the CDLQI, each question on DLQI is scored from 0 to 3 with a maximum score of 30 indicating the worst quality of life. In the original article by Finlay and Khan, scores of those patients with atopic dermatitis indicated poorer quality of life than the scores of patients with other skin diseases assessed by the DLQI. The DLQI has been extensively validated in multiple studies. A 10-year review of the literature found that the DLQI is highly specific for assessing decrements in quality of life in patients with atopic dermatitis. Specifically, patients with atopic eczema had a mean score of 4.2 compared with 0.3 in the disease-free population. The DLQI has high repeatability, internal consistency, and sensitivity to change.
Assessment of health outcomes in atopic dermatitis
Although primarily focused on disease severity and quality of life, the range of potential measurable health outcomes in atopic dermatitis is wide. Disease-severity measurements can include objective clinical parameters that assess degree of erythema, exudation, and excoriations; they can also include subjective criteria such as itching and sleep disturbance. Quality of life is defined as the perception of disease impact on physical, psychological, and social well-being.
Disease-severity scales in atopic dermatitis include disease-specific and non–disease-specific scales. Examples of disease-specific scales include the Severity Scoring of Atopic Dermatitis (SCORAD), Eczema Area and Severity Index (EASI), and Six Area, Six Sign Atopic Dermatitis (SASSAD), while non–disease-specific scales include the Investigators’ Global Assessment (IGA), Total Body Severity Assessment (TBSA), and Visual Analog Scale (VAS). Since the number and type of assessed clinical features vary between scales, a lack of standardization of objective severity scales exists for atopic dermatitis. With some scales assessing multiple body sites while other scales assess only the most severely affected site, diversity exists in the methods of measuring disease extent. Disease-severity scales commonly used in randomized controlled trials (RCTs) of atopic dermatitis treatment include SCORAD, EASI, and IGA. The characteristic features, validity, and reliability of these scales are discussed in the following section.
The SCORAD was developed in 1993 by the European Task Force on Atopic Dermatitis. This scale uses the “rule of nines” to assess disease extent and evaluates 5 clinical characteristics to determine disease severity: (1) erythema, (2) edema/papulation, (3) oozing/crusts, (4) excoriation, and (5) lichenification. The SCORAD also assesses subjective symptoms of pruritus and sleep loss with VAS. Extent of disease, disease severity, and subjective symptoms combine to give a maximum possible score of 103. Although it is a combined score, the three aspects can be separated and used individually if necessary. Of all the severity scales used in atopic dermatitis, the SCORAD is the most widely validated disease-severity instrument. The SCORAD is valid and reliable and has shown excellent agreement with global assessments of disease severity. However, some studies have shown interobserver variation in scoring lichenification and extent of disease.
The EASI was developed by modifying the PASI (Psoriasis Area and Severity Index), a widely accepted and standardized scoring system for psoriasis. The EASI assesses extent of disease at four body sites and measures four clinical signs on a scale of 0 to 3: (1) erythema, (2) induration/papulation, (3) excoriation, and (4) lichenification. The EASI confers a maximum score of 72 and evaluates two dimensions of atopic dermatitis: disease extent and clinical signs. Although some investigators contend that subjective symptoms may be the most important marker for assessing patient morbidity and may act as a good indicator for disease severity, unlike the SCORAD, the EASI does not assess symptoms such as pruritus and sleep loss. In a large validation study with a cohort of 1550 pediatric patients, the EASI was found to have excellent validity, internal consistency, and sensitivity to change. While the EASI is a valid and reliable instrument, most interobserver variability lies in the dimension of induration/papulation.
The IGA allows investigators to assess overall disease severity at one given time point, and it consists of a 6-point severity scale from “clear” to “very severe” disease (0 = clear, 1 = almost clear, 2 = mild disease, 3 = moderate disease, 4 = severe disease, and 5 = very severe disease). The IGA uses clinical characteristics of erythema, infiltration, papulation, oozing, and crusting as guidelines for the overall severity assessment. To the authors’ knowledge, the IGA has not been validated as an outcome measure. However, the IGA has been used to validate other outcome scales. Potential weaknesses of the IGA include lack of responsiveness and discrimination for disease severity and lack of subjective symptoms.
Quality-of-life scales also include both disease-specific and non–disease-specific scales. Instruments specific to atopic dermatitis include the Dermatitis Family Impact (DFI), Parent’s Index of Quality of Life in Atopic Dermatitis (PIQoL-AD), and Quality of Life Index for Atopic Dermatitis (QoLIAD). Non–disease-specific scales include the Dermatology Life Quality Index (DLQI), Children’s Dermatology Life Quality Index (CDLQI), and Infants’ Dermatitis Quality of Life Index (IDQOL). Quality-of-life measurements are increasingly being recognized as important outcome measures but currently are primarily used to supplement existing measurement tools in dermatology. Quality-of-life scales commonly used in RCTs of the treatment of atopic dermatitis are the CDLQI, DFI, and DLQI. The features and validity of these scales are reviewed in the following section.
The CDLQI, which purposes to measure the quality of life in children with skin disease, was developed by Lewis-Jones and Finlay and validated in 1995. The questionnaire was designed for children of ages 4 through 16 years. The CDLQI is completed by the child with assistance from an adult if necessary. The survey consists of 10 questions that evaluate the aspects of a child’s life that could be affected by their skin disease. The instrument includes physical symptoms such as itching and sleep loss and psychosocial questions regarding friendships, bullying, school performance, sports participation, and enjoyment of vacation. The questions are individually graded from 0 to 3 with a maximum possible combined score of 30; the higher scores represent worse quality of life. In the initial validation study, children with atopic eczema accounted for 20% of all patients. To determine test-retest repeatability, the CDLQI was used in a population of children without skin disease.
Since its validation, the CDLQI has been used in numerous studies to determine the effectiveness of interventions in children with atopic dermatitis. The CDLQI has been translated and validated in Cantonese. A cartoon version of the CDLQI, which appears to be quicker and preferred by children, was validated in 2003.
The DFI questionnaire was developed in 1998 by Lawson, Lewis-Jones, Finlay, Reid, and Owens to help measure how family life is affected by a child suffering from atopic dermatitis. The DFI is designed to be completed by a caretaker of the child, who is often the parent. It consists of 10 questions related to housework, food preparation and feeding, sleep, family leisure activity, shopping, fatigue, emotional distress, and relationships. Each question is graded from 0 to 3 with a maximum combined score of 30. The DFI was deemed valid, reliable, and sensitive to change in multiple studies. Two of the studies assessing validity of the instrument used the separate components of the DFI instead of the total score as was originally intended. The DFI has also been validated in Malay and Portuguese.
The DLQI was developed in 1994 by Finlay and Khan to measure quality of life in adults older than 18 years in routine clinical-practice settings. The DLQI is a 10-item questionnaire that evaluates skin symptoms, feelings of embarrassment, and how skin disease has affected day-to-day activities, working life, and social life. Similar to the CDLQI, each question on DLQI is scored from 0 to 3 with a maximum score of 30 indicating the worst quality of life. In the original article by Finlay and Khan, scores of those patients with atopic dermatitis indicated poorer quality of life than the scores of patients with other skin diseases assessed by the DLQI. The DLQI has been extensively validated in multiple studies. A 10-year review of the literature found that the DLQI is highly specific for assessing decrements in quality of life in patients with atopic dermatitis. Specifically, patients with atopic eczema had a mean score of 4.2 compared with 0.3 in the disease-free population. The DLQI has high repeatability, internal consistency, and sensitivity to change.
Results of health outcomes in atopic dermatitis
Atopic dermatitis makes a significant impact on patients’ quality of life given its potential long-term physical, social, and psychological impairments. In children suffering from atopic dermatitis, 60% of the parents reported that their child had difficulties with school performance and with social and leisure activities. Scratching has been associated with disturbed sleep patterns, including difficulty in getting to sleep, frequent night-time wakening, reduced total sleep, and difficulty awakening for school. Children rate itching and sleep loss as the most bothersome aspect of their disease. Sleep loss can lead to daytime behavior and discipline problems. Daud and colleagues showed that 23% of preschool children had a significant increase in behavioral symptoms compared with 5% of controls. Children also experience teasing and bullying from the appearance of atopic dermatitis lesions, which may lead to embarrassment, loss of confidence, mood changes, and depression.
The family members of children with atopic dermatitis can likewise suffer decrements in quality of life. Parents may lose an average of 2.5 hours of sleep per night, while 38% of siblings of children with atopic dermatitis experienced disturbed sleep. Physical and mental exhaustion from sleep loss causes mood changes and impaired performance at school or work for family members. Caring for a child with atopic dermatitis can cause parents to miss work and suffer financial losses. When a child in the family is diagnosed with atopic dermatitis, families may experience lifestyle restrictions, including dietary limitations, vacation choices, and pet ownership. Ninety percent of families reported problems with household issues such as laundry, cleaning, and food preparation. Parents may also suffer psychological distress from hearing others comment negatively about their child’s appearance.
In a study using the DLQI and another quality-of-life instrument, the SF-36 (Short Form Health Survey), adult patients with atopic dermatitis were found to have significantly impaired quality of life in comparison with the general United States population in the vitality, social functioning, and mental health dimensions of the SF-36. Atopic dermatitis patients had similar DLQI scores to patients with other chronic dermatologic diseases. When compared specifically with psoriasis, atopic dermatitis patients had lower scores in vitality, social functioning, role-emotional, role-physical, and mental health. When compared with other nondermatologic chronic diseases such as diabetes and hypertension, atopic dermatitis patients had lower mental health scores. A correlation also existed between increased severity of atopic dermatitis and greater impairments in quality of life.
Gender differences appear to play a role in the psychological impact of atopic dermatitis. With similar levels of disease severity, women with atopic dermatitis report a poorer quality of life than men. Women with visible skin lesions report more social anxiety, helplessness, and anxious-depressive symptoms than men.
Atopic dermatitis can also have an impact on patient-partner relationships. In a study investigating the sexual life of atopic dermatitis patients and their partners, 57.5% of patients reported a decrease in sexual desire due to atopic dermatitis, with 36.5% reporting that the appearance of eczema had an impact on their sex life.
Treatment of atopic dermatitis and its effect on health outcomes
The symptoms of atopic dermatitis can be controlled with both topical and oral medications. Treatment is aimed at reducing skin inflammation and controlling pruritus. The general categories of therapy for mild to moderate atopic dermatitis include emollients, topical steroids, topical calcineurin inhibitors, oral antihistamines, phototherapy, probiotics, and educational support. The most common treatment is a combination of an emollient and corticosteroid. The following section presents the most common treatment options for atopic dermatitis, the evidence for their efficacy, and the effect of treatment on health outcome measures.
Emollients
Skin hydration is an important component of the treatment of atopic dermatitis, as xerosis is a hallmark of the disease. Maintaining hydration is often achieved by ample lubrication of the skin with emollients. Emollients also have a steroid-sparing effect in the treatment of atopic dermatitis. In a study done in infants with atopic dermatitis, emollients decreased the need for moderate-potency or high-potency topical corticosteroids. The study evaluated the effect of an oat extract–containing emollient on the amount of topical steroid used; the intervention group decreased steroid use by 42%, while the control group decreased use by 7.5%. In addition to comparing the amount of corticosteroid used, disease severity and quality of life of the infant and parent was evaluated. Disease severity was assessed with the SCORAD. Infant’s and parent’s quality of life was assessed using the IDQOL and DFI, respectively. All aspects of the SCORAD significantly improved for both treatment groups. However, the only significant difference in symptom relief between treatment groups was dryness, which was decreased in the emollient group. Both groups showed highly significant improvement in the quality of life for infants and parents. Comparing the two treatment groups, the only significant difference included the sleep item in the DFI score, which was better in the emollient group than in the control group.
In another study, a new emollient containing 2% Sunflower oil Oleodistillate (SO) was tested for its steroid-sparing effect. Disease severity and quality of life were also assessed with the SCORAD and IDQOL/DFI, respectively. The components of the SCORAD that improved significantly among all groups were lichenification and excoriation. The study showed that application of steroid every other day with the SO cream was as effective as once or twice daily application of the steroid alone; these findings suggest that the new emollient provided a steroid-sparing effect. According to the IDQOL, parents reported a large improvement in quality of life for children who were treated with SO cream and any dose of steroid. Furthermore, parents of children receiving SO cream in combination with topical steroids reported a greater improvement in DFI scores compared with parents of children receiving steroid cream without SO cream.
Topical Corticosteroids
Topical corticosteroids are a mainstay of treatment in atopic dermatitis. Steroids of different potency are used based on the severity of disease. Low-potency topical steroids are effective for mild disease, whereas high-potency topical corticosteroids can be in used in patients with acute flares. High-potency corticosteroids are avoided in sensitive areas such as the face and skin folds. Topical steroids can be used multiple times a day, but no clear benefit has been shown for more frequent use than once daily.
Various formulations of corticosteroids have been shown to be efficacious in the treatment of atopic dermatitis. For example, a review of two RCTs using 0.05% halobetasol propionate (HP) ointment twice daily for 2 weeks showed an improvement in symptoms scores in the HP group compared with the placebo group. One RCT used the Physician’s Global Assessment (PGA) to evaluate overall disease severity and showed a significant improvement in the HP group over the placebo group, with 38% of patients in the HP group completely resolving their lesions compared to 6.5% in the placebo group. Another study that also used the PGA to assess disease severity tested clobetasol propionate (CP) emollient cream 0.05% in a 4-week RCT. Patients with moderate to severe atopic dermatitis were treated with CP cream twice daily for 4 weeks. PGA scores were improved in the treatment group in comparison with the placebo group by day 4 and remained improved throughout the treatment period.
Topical steroids can also be used in maintenance therapy to help prevent relapse. In a study in adults with atopic dermatitis, long-term management for recurring atopic dermatitis was studied using fluticasone propionate (FP) ointment. All patients were initially treated with FP 0.005% ointment. Those who achieved clearance or near clearance then entered one of two long-term treatment categories: either FP or placebo ointment once daily, twice a week for 16 weeks to healed lesions. Efficacy was measured using the SCORAD. At the end of the initial treatment, SCORAD values were significantly improved. After the maintenance phase, the FP group maintained their improvement from baseline, but the placebo group deteriorated.
FP 0.005% ointment was also tested in children for maintenance therapy. Children with moderate to severe atopic dermatitis were treated initially with FP ointment. Those who entered remission were subsequently treated twice weekly with either FP or placebo ointment for 16 weeks to test prevention of exacerbations. A decrease in disease severity was observed at the end of the initial treatment phase. SCORAD values increased in both the FP and placebo group after the maintenance phase. However, the scores from the FP group increased to a lesser degree than the placebo group’s scores. The risk of exacerbation was also calculated with hazard ratios using a target lesion score, and the risk was found to be more than twice as high in the placebo group than in the FP group, which demonstrates that FP maintenance therapy reduces the risk of disease relapse in children with atopic dermatitis.
Maintenance therapy with topical corticosteroids has also been shown to improve quality of life in patients with atopic dermatitis. In a study testing methylprednisolone aceponate (MPA) cream twice weekly for 16 weeks in patients 12 years of age or older, investigators examined intensity of itch, quality of sleep, and overall quality of life. The total DLQI and CDLQI scores improved with MPA treatment and worsened in all categories in the placebo group. While intensity of itch decreased in both groups, the improvement was more substantial in the MPA group than in the placebo group.
Topical Calcineurin Inhibitors
Topical calcineurin inhibitors are a class of steroid-sparing medications effective for the treatment of atopic dermatitis. One advantage of calcineurin inhibitors is that they do not cause skin atrophy, a side effect which can be observed with long-term topical steroid use. Two calcineurin inhibitors approved by the Food and Drug Administration for use in children older than 2 years are tacrolimus and pimecrolimus. These two topical calcineurin inhibitors are considered equivalent in strength to low-potency topical steroids and are both applied twice a day. Calcineurin inhibitors are second-line agents; mid-potency to high-potency topical steroids exhibit greater clinical efficacy and are therefore preferred as first-line agents. In a study comparing the efficacy of MPA ointment 0.1% with that of tacrolimus 0.03% in children and adolescents with an acute atopic dermatitis flare, a significantly greater mean percentage improvement from baseline was found in the MPA group compared with tacrolimus, as measured by the EASI. Results for the CDLQI also showed greater improvement in the MPA group in comparison with the tacrolimus group in the categories of “symptoms and feelings” and “sleep.”
Topical tacrolimus has been shown to be an effective alternative to topical steroids, and its efficacy has been shown in several RCTs. Specifically, studies measuring disease severity by the EASI in both adult and pediatric patients have shown significantly greater improvement in tacrolimus treatment groups compared with placebo groups. Tacrolimus has also been shown to improve quality of life in patients with atopic dermatitis. In a study comparing two concentrations of tacrolimus ointment (0.03% and 0.1%) versus placebo, both adult and pediatric quality of life was evaluated. Adult quality of life was evaluated using the DLQI, and pediatric quality of life was evaluated using the CDLQI. Quality of life was assessed at baseline, 3 weeks, and at the end of the trial at 12 weeks. Results showed a significant improvement among adults in both tacrolimus groups in comparison with the placebo group and in all aspects of quality of life. In the pediatric patients, both tacrolimus groups demonstrated significant improvements in quality of life in all aspects, except for personal relationships. In a long-term study of maintenance treatment with 0.1% tacrolimus ointment in adults, quality of life was measured using the EQ-5D. Patients were treated twice daily with tacrolimus ointment for 6 weeks and were subsequently treated with either tacrolimus ointment or emollient vehicle twice weekly for 1 year. Results showed initial treatment with tacrolimus ointment significantly improved quality of life for adults with moderate and severe atopic dermatitis. The improvement was sustained over the 1-year maintenance period.
Pimecrolimus has a similar mechanism of action to tacrolimus. Pimecrolimus is effective in treating atopic dermatitis but does not have systemic immune effects. Pimecrolimus is also effective in reducing the need for topical steroids and preventing atopic dermatitis flares. Several studies have assessed the effects of pimecrolimus treatment on disease severity and quality of life in patients with atopic dermatitis. In adolescents and adults, disease severity was measured using the EASI and IGA in two studies. The first study investigated the efficacy of pimecrolimus cream 1%, twice daily and four times daily to all affected areas in patients with moderate to severe atopic dermatitis. Both groups improved in IGA and EASI scores, with no statistical difference between groups. In the second study, pimecrolimus cream 1% was tested in the head and neck of patients older than 12 years with mild to moderate atopic dermatitis. Results showed a significant improvement in IGA and head and neck EASI scores. Of note, compared to those patients treated with placebo, significantly more patients treated with pimecrolimus achieved clearance of their eyelid dermatitis. Studies in children and infants have also shown greater improvement in the EASI and IGA scores of patients using pimecrolimus than those using placebo.
In quality-of-life studies, pimecrolimus has been shown to improve parents’ quality of life. In two studies, the PIQoL-AD was used to assess parents’ quality of life after treatment with pimecrolimus cream. In the first study, pediatric patients were treated with pimecrolimus cream 1% for 24 weeks. Results showed a significant improvement in parents’ quality of life compared with the control group after acute and after long-term treatment. In the second study, also done in a pediatric population, pimecrolimus cream 1% was given for 26 weeks. Parents’ quality of life was assessed at baseline, 6 weeks, and 6 months. Results showed a statistically significant improvement in PIQoL-AD scores at 6 weeks and 6 months. In a study in infants with mild to severe atopic dermatitis, parents’ quality of life was measured by the PQoL-AD after 4 weeks of treatment with pimecrolimus. Results showed an improvement in all 5 areas of the questionnaire, including psychosomatic well-being, effects on social life, confidence in medical treatment, emotional coping, and acceptance of disease.
Oral Antihistamines
Oral antihistamines are often used in the treatment of atopic dermatitis as an adjunctive therapy for pruritus. However, the studies testing antihistamines have shown conflicting results. In a study in 2006, 20 adult patients with moderate atopic dermatitis who had not received any treatment for two weeks were randomized to the second-generation antihistamine, fexofenadine, and either emollient treatment or steroid treatment for 1 week. Disease severity was assessed with the SCORAD and VAS for pruritus before and after treatment. Results showed a significant improvement in both instruments for both treatment groups, suggesting antihistamine therapy reduces pruritus in adult atopic dermatitis patients.
Other antihistamines have been shown in small trials to be effective in atopic dermatitis patients complaining of pruritis. Langeland and colleagues conducted a study of loratadine in 16 adult patients with moderate or severe atopic dermatitis. Patients were randomized to either 10 mg loratadine or placebo once daily, alternating between loratadine and placebo every 2 weeks. Pruritus was assessed twice a day by the patients using a VAS. Results showed a significant improvement in pruritus during loratadine treatment during the day and at the end of each treatment period. However, the effect of loratadine on pruritus during the night was not statistically significant. Doherty and colleagues conducted a study in 49 adult atopic dermatitis patients who were randomized to 10-day courses of 8 mg acrivastine, 60 mg terfenadine, or placebo. Both drugs are selective H1 histamine receptor blockers with no major sedative effects. Results showed a statistically significant improvement in pruritus with both acrivastine and terfenadine and no significant differences between groups. However, it is difficult to compare these two interventions because acrivastine was measured using a doctor’s assessment and terfenadine was measured using a VAS.
Multiple studies show the ineffectiveness of antihistamines in treating pruritus in patients with atopic dermatitis. Wahlgren and colleagues conducted an RCT using both a sedative (clemastine) and nonsedative (terfenadine) antihistamine in 25 adult patients with atopic dermatitis. Itch was assessed using a VAS after 3 days of treatment with either clemastine 2 mg twice a day, terfenadine 60 mg twice a day, or placebo. Results showed no significant differences in itch intensity between groups. Berth-Jones and Graham-Brown conducted a RCT using terfenadine 120 mg twice a day for 1 week for the treatment of pruritus in patients with chronic atopic dermatitis. Patient-recorded VAS scores showed no improvement in severity of pruritus. To determine whether antihistamines are effective in the treatment of pruritus in atopic dermatitis patients, large randomized placebo-controlled trials are needed.
Phototherapy
Phototherapy has been shown to be effective in the treatment of atopic dermatitis. Multiple types of ultraviolet (UV) light therapy are effective, including psoralen-UVA, broadband UVA, broadband UVB, combined UVA and UVB, narrow-band UVB, and UVA1. In a study comparing high-dose UVA1 therapy with UVA-UVB or topical glucocorticoid therapy in patients with acute, severe atopic dermatitis, significantly greater improvement in Costa scores was observed with the UVA1 and glucocorticoid group compared with the UVA-UVB group after 10 days of treatment. Another study comparing the efficacy of medium-dose UVA1 versus narrow-band UVB assessed clinical disease and quality of life using the SASSAD and the Skindex-29 (a 29-item self-administered questionnaire), respectively. Twenty-eight patients completed the 6-week study. Results showed a significant improvement in SASSAD scores in both groups with no significant difference between groups. No significant improvement in Skindex-29 scores was seen in either treatment group. Majoie and colleagues also conducted a study in 13 adult patients comparing medium-dose UVA1 and narrow-band UVB. Results from that study showed a significant improvement in disease severity in both treatment groups using the Leicester Sign Score (LSS). In a study of UVB-only phototherapy, 20 patients were treated with either a conventional fixed dosing regimen or varying dosages based on skin pigmentation and erythema. Results showed a decrease in clinical severity of disease as measured by the SCORAD in both groups, but no significant difference existed between treatment groups. However, final UVB dosage and cumulative UVB dosage was significantly lower in the group receiving the optimized dose. Phototherapy can also be used in combination with other forms of therapy for atopic dermatitis, such as corticosteroids. In a study comparing the efficacy of UVA/UVB treatment with UVA/UVB plus topical corticosteroid therapy, Costa scores showed significant improvement in both groups. Although no significant difference was noted between groups, improvement appeared earlier in the UVA/UVB plus corticosteroid group, which reduced the total UVB dose and duration of treatment. Although UV light therapy is effective, this treatment modality is limited to severe cases of atopic dermatitis because of the cost and increased risk of skin cancer.
Probiotics
Probiotic therapy with Lactobacillus and other live strains has been studied for the treatment of atopic dermatitis, since patients with atopic dermatitis possess different gut bacteria than patients without the disease. Suggested mechanisms of action include a reduction of intestinal inflammation and permeability, which leads to a decrease in antigen presentation in gut lymphoid tissue. In two recent reviews of probiotic therapy in the treatment of atopic dermatitis, evidence to support probiotic therapy was lacking. In a Cochrane review by Boyle and colleagues, 12 RCTs examining the efficacy of probiotics compared to placebo showed no statistically significant improvements in disease severity based on measurements by SCORAD. Three studies using Lactobacillus rhamnosus strain GG demonstrated an increase in disease severity, but results for all other Lactobacillus strains showed a decrease in disease severity. Therefore, it is possible that specific probiotic strains might show benefit. In another systematic review by Michail and colleagues, 11 of the 12 studies from the review by Boyle and colleagues were included. However, Michail and colleagues were able to obtain unpublished SCORAD values for 10 of the studies previously reviewed by Boyle and colleagues. Although Michail and colleagues reported a statistically significant reduction in mean SCORAD values in the probiotic group compared with the placebo group, the small difference may be of limited clinical significance.
Two studies assessed quality of life during treatment with probiotics. Weston and colleagues used the DFI to assess quality of life in families of children with atopic dermatitis. Fifty-six children with moderate or severe atopic dermatitis were randomized to receive either Lactobacillus fermentum twice daily for 8 weeks or placebo. Quality of life was assessed at the end of intervention (8 weeks) and after an 8-week follow-up period (16 weeks). Median DFI scores improved in both groups at both time periods, but the statistical significance was not mentioned. No differences existed between groups at 8 weeks, but at 16 weeks the median DFI score was −2.5 in the probiotic group versus −3.0 in the placebo group. Fölster-Holst and colleagues used a different published scale to assess quality of life in patients treated with probiotics. The scale assessed different aspects of quality of life including psychosomatic well-being, effects on social life, satisfaction with medical care, dealing emotionally with the illness, and acceptance of the disease. Fifty-four infants with moderate to severe atopic dermatitis were randomized to daily L rhamnosus strain (GG) or placebo for 8 weeks. Results showed no significant difference in quality-of-life scores from baseline to 8 weeks in either treatment group. In addition, no statistical difference existed between treatment groups.
Psychological and Educational Interventions
Multiple studies have shown that psychological treatment of atopic dermatitis can reduce the anxiety level for both patients and families and decrease the amount of medications necessary to control the disease. Specifically, individual psychotherapy, group therapy, and educational programs have shown benefit in atopic dermatitis. Linnet and Jemec used the Spielberger State-Trait Anxiety Index (STAI) to assess anxiety levels in adult patients with mild to severe atopic dermatitis after 6 months of either brief dynamic psychotherapy or no treatment. After post hoc multiple regression, atopic dermatitis patients with a higher level of trait anxiety at baseline showed a greater improvement in anxiety level after psychotherapy.
Group therapy not only can improve the quality of life of patients and their families, but can also improve disease severity and lead to better treatment adherence. In a study by Weber and colleagues, the quality of life of children with atopic dermatitis and their families was studied using the CDLQI and DFI after they had joined support groups. The patient-parent family unit was randomized to either 6 months of group therapy with one meeting every 2 weeks or no psychotherapy. Results showed a significant improvement in CDLQI scores in the intervention group in comparison with the control group. However, DFI scores showed no improvement after treatment.
Video-based education is another option for provision of educational counseling to patients. In a study by Armstrong and colleagues, online video-based patient education was compared to written pamphlet education in a randomized control trial. Eighty adult atopic dermatitis patients were given identical information about atopic dermatitis and its management in either video format or written pamphlet form. Knowledge of atopic dermatitis was assessed with standardized questionnaires and atopic dermatitis disease severity was measured by the Patient-Oriented Eczema Measure (POEM). Results showed a significantly greater increase in atopic dermatitis knowledge in the video group over the pamphlet group, along with greater improvements in clinical outcome as measured by the POEM.
Educational counseling has shown conflicting results. In a study of a single 15-minute educational session with an atopic dermatitis educator, Shaw and colleagues showed no significant difference in CDLQI and IDQOL scores. In a study using a 30-minute session which included instruction and demonstration of techniques for applying medication by a trained dermatology nurse, no significant differences between intervention and control groups in CDLQI, IDQOL, or DFI mean scores were reported. However, with more extensive interventions, improvement was seen with educational programs. Grillo and colleagues conducted a study of a 2-hour workshop, which included education and a practical session on wet wrapping and cream application. CDLQI, IDQOL, and DFI were assessed at 4 and 12 weeks after intervention. Results showed an improvement in all scores in both treatment groups. However, a significant difference between treatment and control group existed only for mean CDLQI scores at 12 weeks. More definitive results were shown by Staab and colleagues in a study of an age-specific educational program for children and adolescents. The education program involved 6 2-hour sessions held once a week. The sessions covered medical, nutritional, and psychological issues. Quality of life was assessed with a German questionnaire called “Quality of life in parents of children with atopic dermatitis.” The instrument included questions related to 5 different topics: psychosomatic well-being, effects on social life, confidence in medical treatment, emotional coping, and acceptance of the disease. Results showed that parents who had children younger than 7 years experienced a significant improvement in quality of life for all 5 subscales, and parents with children aged 8 to 12 years showed significant improvement in 3 of 5 subscales (including confidence in medical treatment, emotional coping, and acceptance of the disease).
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