Clinical Signs Of Atopic Dermatitis Research Articles

Effects of a pH-Regulating Emollient Cream in Mild Atopic Dermatitis Patients with Moderate Localized Lesions

Introduction: Increased skin pH values in patients with atopic dermatitis (AD) contribute to poor antimicrobial and permeability barrier functions of the skin. In practice, the majority of topical preparations available for dry skin conditions do not provide sufficient pH and buffering capacity for maintaining optimum skin surface conditions. To address this issue, we tested a novel zinc lactobionate preparation to determine whether the regular application would lower skin surface pH, and in doing so improve the condition of lesional skin. Methods: The assessment for local severity of AD was done with the Scoring Atopic Dermatitis Index (SCORAD) and skin dryness was assessed by capacitance measurement. Results: The results showed that the test product lowered skin pH and improved AD skin lesions from moderate to mild during 2 weeks of application. In the treated area a lowered pH of about 0.85 units was found. Together with the lowering of pH, the local SCORAD significantly improved from 8.3 on average down to 4.0, while in the untreated area, only a slight improvement (from 8.2 to 6.4) was found. Conclusion: Synergistic effects of the test product’s pH lowering and emollient properties might explain the observed improvements in clinical signs of AD and further research against a comparator would allow the specific contribution of pH modulation to these improvements to be unambiguously isolated.

The Eczema Area and Severity Index: An update of progress and challenges in its measurement of atopic dermatitis after 20 years of use.

The Eczema Area and Severity Index is an investigator-assessed instrument reporting clinical signs of atopic dermatitis. The instrument is extensively validated in both adult and paediatric populations and recommended as a core outcome measure to assess clinical signs by the Harmonising Outcome Measures for Eczema initiative in clinical trials and was recently recommended as an option to measure signs in clinical practice. Here, we review the validation of the instrument using standard assessment criteria, explore controversies and challenges to its universal applicability and highlight future electronic adaptations. We find that the instrument demonstrates adequate performance in the measurement properties recommended by the COnsensus-based Standards for the selection of health Measurement INstruments initiative for instruments reporting clinical signs, is clinically interpretable, and is suitable for all atopic dermatitis severities. Some validation gaps remain. Information reporting on its performance in diverse populations, with emphasis on deeply pigmented skin, is promising though limited. Technological adaptations are demonstrating promising initial validation results and may facilitate remote and/or automated assessments assisting clinical care and decentralized clinical trials in the future. We find no strong evidence limiting its use in trials or clinical practice although questions pertaining to the effect of investigator training remain. We recommend that the Eczema Area and Severity Index be used in all interventional atopic dermatitis trials and be considered alongside other recommended clinical practice severity instruments.

Improvement effects of tapinarof on the skin barrier function in Japanese patients with atopic dermatitis

Background: Tapinarof is a nonsteroidal, topical, aryl hydrocarbon receptor agonist. Tapinarof has been shown to be efficacious and have acceptable safety profile in the treatment of atopic dermatitis (AD).Objective: We sought to evaluate the improvement effect of tapinarof on skin barrier function in patients with AD.Methods: This was an open-label, uncontrolled, single-center study. Japanese patients aged ≥20 years with AD (N = 30) were included in this study. Patients applied tapinarof cream 1% once daily to the target areas on the volar forearm for 8 weeks. The primary endpoints were changes from baseline in stratum corneum hydration (SCH) and transepidermal water loss (TEWL) at the target affected area at week 8.Results: The mean SCH value at the target affected area was 13.656 AU at baseline, 16.904 AU at week 4, and 16.423 AU at week 8. The SCH at the target affected area significantly increased from baseline to week 8, with a mean change of 2.826 AU (p = 0.0433). The mean TEWL value at the target affected area was 17.35 g/m2/hr at baseline, 10.01 g/m2/hr at week 4, and 9.52 g/m2/hr at week 8. The TEWL at the target affected area significantly decreased from baseline to week 8, with a mean change of −8.03 g/m2/hr (p < 0.0001). Clinical signs of AD at the target affected area were improved over time. No serious, severe, or treatment-related AEs were reported.Conclusion: Treatment with tapinarof led to an increase in SCH and a decrease in TEWL in patients with AD, indicating the potential improvement effect of tapinarof on skin barrier function.

The safety of rush immunotherapy in the management of canine atopic dermatitis-230 cases.

The duration of the induction phase of allergen-specific immunotherapy conventionally is a period of several weeks, during which the volume of an allergen solution, administered by injection, is gradually increased until the maintenance dose is reached. In rush immunotherapy (RIT), the induction period is abbreviated to achieve a faster improvement in clinical signs of atopic dermatitis (AD) compared to conventional immunotherapy. The aim of this retrospective study was to evaluate the safety of RIT in 230 dogs with AD and report any adverse effects (AE). Two hundred thirty client-owned dogs. Medical records of dogs receiving RIT between 2012 and 2021 were analysed and observed AE were investigated. All dogs underwent RIT following a protocol of subcutaneous allergen extract injections, given hourly with an incrementally increasing volume from 0.1 to 1.0 mL. Adverse effects were documented in 6 of 230 (2.6%) dogs. Five of these dogs (2.2%) showed mild gastrointestinal signs (1 of 5 vomiting, 4 of 5 diarrhoea) and one patient an increase in body temperature by 1.5°C. These occurred at different stages of the RIT protocol. All AE were graded as mild and self-limiting. Based on these data, supervised RIT in dogs appears to be a safe procedure to achieve the maintenance dose of allergen immunotherapy earlier with infrequent and mild AE.

The use of hydrolyzed formulas as a method of correction of feeding and clinical rehabilitation of infants with atopy signs

Our study showed that in formula-fed babies, the use of mixture X (containing 2'-FL (2'-fucosyllactose) - a type of milk oligosaccharide, as well as carefully studied Bifidobacterium lactis, DHA, ARA, and nucleotides) as the main product for feeding could ensure children's body with all the necessary nutrients. Furthermore, it can minimize the progression of clinical signs of atopic dermatitis and reduce the use of drugs. In addition, there was an improvement in height and weight parameters, proportional development of the child (p<0.05), an increase in the number of erythrocytes (erythrocytes), hemoglobin (Hb), mean cell volume (MCV) (p<0.05), a decrease in the number of leukocytes (WBC) (p<0.05), and leveling of skin signs of atopic dermatitis (AD) (according to SCORAD a decrease from 32.8±5.5 to 16.1±2.2, p<0.05). Based on these results, it is possible to recommend using mixture (X) with a preventive and rational purpose as a product of artificial feeding of children with a hereditary predisposition to allergies.

Janus kinase inhibitors for the treatment of atopic dermatitis-evaluation of current data and practical experience

Atopic dermatitis is acommon chronic inflammatory skin disease and has amajor impact on patient's quality of life. Janus kinase inhibitors were recently approved for the treatment of atopic dermatitis. To summarize current data on efficacy and safety of Janus kinase inhibitors for the treatment of atopic dermatitis as well as guidelines for the use in clinical practice. Summary and assessment of currently available data. Three Janus kinase inhibitors are approved for the treatment of moderate to severe atopic dermatitis: baricitinib, upadacitinib and abrocitinib. Clinical trials and first real-life data demonstrate rapid and strong reduction of pruritus and clinical signs of atopic dermatitis as well as improvement of patient's quality of life. The safety profile is favorable, although data on long-term safety especially for the treatment of atopic dermatitis patients are still lacking. Janus kinase inhibitors enrich the therapeutic portfolio for the treatment of atopic dermatitis. When carefully taking into consideration contraindications, side effects, and necessary laboratory controls, they represent ahighly effective and safe treatment option for affected patients.

Validity of the epidemiology of atopic dermatitis is questionable

Today, the prevalence rates of atopic dermatitis are very different worldwide. Epidemiological data are primarily influenced by factors such as the lack of a unified approach to the definition of the disease, study design, disease codes, diagnosis, research methods, etc. In addition, it is important what is the severity of atopic dermatitis and the accuracy of the diagnosis. The use of records in electronic records and prescribed prescriptions also indicate insufficiently accurate identification of such patients. It is necessary to clarify the clinical signs of atopic dermatitis, and the codes of diseases, including those misdiagnosed as atopic dermatitis, which directly affects the epidemiology of this disease.

Randomized, double-blind, placebo-controlled clinical trial measuring the effect of a dietetic food on dermatologic scoring and pruritus in dogs with atopic dermatitis

BackgroundCanine atopic dermatitis (AD) is a common condition that often requires multimodal therapy. Including a diet in the multimodal management of AD may reduce medication doses, saving pet owners money and reducing side effects. The objective of this randomized, double-blind, placebo-controlled clinical trial was to determine if a diet fortified in antioxidants, polyphenols, and omega-3 fatty acids can reduce the clinical signs of AD. Forty client-owned dogs with AD were enrolled in the study and assigned to either an enriched diet (diet B) or control diet (diet A) for 60-days. CADESI-4 index scores and owner-reported pruritus scores were measured periodically.ResultsTotal CADESI-4 index scores for dogs eating diet B were lower on day 60 compared to baseline (P = 0.003). There was no statistical difference in scores for dogs eating diet A over a 60-day period. Diet B dogs had 25 and 49% reductions in CADESI-4 index scores on days 30 and 60, respectively (P = 0.0007) while diet A had no change over the study period. When comparing the percent change in owner-reported pruritus scores, diet B also performed better than diet A. By day 60, owners feeding diet B to their dogs reported a significant reduction (P < 0.0001) of 46.4% in itching, while those on diet A reported a 26.8% reduction, which was not statistically significant (P = 0.08).ConclusionsThese study results demonstrate feeding a diet enriched with ingredients to improve skin health and reduce inflammation improves the clinical signs of AD in dogs.

Dupilumab use in atopic dermatitis and beyond in skin diseases.

Atopic dermatitis (AD) is a chronic inflammatory condition that affects 5-10% of adults and 9-18% of children and its pathology is rooted in the Th-2-mediated immune response. Dupilumab is a fully human IgG4 monoclonal antibody that targets the IL-4 receptor alpha subunit that is endogenously bound by the Th-2 cytokines IL-4 and IL-13. Successful clinical trials of dupilumab showing marked improvements in clinical signs of AD, patient reported symptoms and quality of life measures led to its approval for clinical use for moderate-to-severe AD in 2017. This review details the current body of evidence on the drug's mechanism of action, pharmacology, clinical efficacy and safety as well as post market and real world use.

Systemic Immunomodulatory Treatments for Patients With Atopic Dermatitis

Most clinical trials assessing systemic immunomodulatory treatments for patients with atopic dermatitis are placebo-controlled. To compare the effectiveness and safety of systemic immunomodulatory treatments for patients with atopic dermatitis in a systematic review and network meta-analysis. The Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Latin American and Caribbean Health Science Information database, Global Resource of Eczema Trials database, and clinical trial registries were searched from inception to October 28, 2019. English-language randomized clinical trials of 8 weeks or more of treatment with systemic immunomodulatory medications for moderate to severe atopic dermatitis were included. Titles, abstracts, and articles were screened in duplicate. Of 10 324 citations, 39 trials were included. Data were extracted in duplicate, and the review adhered to Preferred Reporting Items for Systematic Reviews and Meta-analyses for Network Meta-Analyses guidelines. Random-effects bayesian network meta-analyses were performed and certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation criteria. Prespecified outcomes were change in signs of disease, symptoms, quality of life, itch, withdrawals, and serious adverse events. A total of 39 trials with 6360 patients examining 20 medications and placebo were included. Most trials were conducted for adults receiving up to 16 weeks of therapy. Dupilumab, 300 mg every 2 weeks, was associated with improvement in the Eczema Area and Severity Index score vs placebo (mean difference, 11.3-point reduction; 95% credible interval [CrI], 9.7-13.1 [high certainty]). Cyclosporine (standardized mean difference, -1.1; 95% CrI, -1.7 to -0.5 [low certainty]) and dupilumab (standardized mean difference, -0.9; 95% CrI, -1.0 to -0.8 [high certainty]) were similarly effective vs placebo in clearing clinical signs of atopic dermatitis and may be superior to methotrexate (standardized mean difference, -0.6; 95% CrI, -1.1 to 0.0 [low certainty]) and azathioprine (standardized mean difference, -0.4; 95% CrI, -0.8 to -0.1 [low certainty]). Several investigational medications for atopic dermatitis are promising, but data to date are limited to small early-phase trials. Safety analyses were limited by low event rates. Dupilumab and cyclosporine may be more effective for up to 16 weeks of treatment than methotrexate and azathioprine for treating adult patients with atopic dermatitis. More studies directly comparing established and novel treatments beyond 16 weeks are needed and will be incorporated into future updates of this review.

Efficiency and tolerability of drug AEvit in complex treatment of patients with atopic dermatitis

Objective — to evaluate the effectiveness and tolerability of drug AEvit in the complex treatment of patients with atopic dermatitis (AD).Materials and methods. We observed 100 patients with AD, who were randomized into the main (50 patients) and control (50 patients) groups. Demographic and anamnestic data were collected from all patients, clinical signs of AD on the SCORAD (Severity scoring of atopic dermatitis: Consensus Report of the European Task Force on Аtopic Dermatitis) scale were evaluated, general clinical biochemical studies were performed. Inclusion criteria were: male and female gender, age from 18 to 70 years, diagnosis of AD in the stage of exacerbation established on the basis of the criteria of Hanifin and Rajka1; moderate or severe degree of the disease (30—70 points on the SCORAD scale); affected area &lt; 30 % of the body surface. Patients underwent standard therapy. Patients of the main group additionally took AEvit, 1 capsule per day after meals for 30 days. Statistical processing of the obtained results was carried out with the use of methods of biometric analysis implemented in the packages of licensed programs Excel 2003 and Statistica 6.1 (StatSoft Inc., serial number AGAR909E415822FA).Results and discussion. Analysis of the anamnestic data allowed establishing the duration of the disease: up to 1 year — in 27 patients, 1—5 years — in 45 patients, 5—10 years — in 21 patients, more than 10 years — in 7 patients. There were 35 (35 %) men and 65 (65 %) women among the examined patients with AD. The duration of the disease according to the anamnestic history was 52.8 years in the main group, and 4.18 — in the control group. After the course of treatment, 28 (56 %) patients of the main group and 19 (38 %) patients of the control group achieved complete clinical remission of the disease. In all other cases, a significant reduction in the SCORAD index was achieved.Conclusions. There was a statistically significant decrease in the severity of the symptoms of the disease in both groups, but it was much more pronounced in the group of patients who used AEvit in the complex treatment.

ETIOPATHOGENETIC FEATURES OF ATOPIC DERMATITIS IN PRESCHOOL CHILDREN

Objective. To determine the most important etiopathogenetic factors of formation, with their subsequent influence on the severity of atopic dermatitis (AD) in preschool children. Material and methods. 58 children aged 2 to 5 years with AD were examined. Clinical examination of patients, a general analysis of blood and urine, koproovocystoscopy, the determination of specific IgE (to food, household, epidermal, pollen allergens) by ELISA, examination of feces for dysbiosis were performed. Assessment of clinical manifestations of AD was carried out on the bases of the SCORAD system (1997). Results. The obtained data indicated that in the severe course of the disease the first clinical signs of AD were observed already in early childhood (up to a year). Hereditary burden for allergic diseases was determined on average 74.1%, but with moderate and severe pollen sensitization was recorded - in 46.6%, epidermal - in 13.8% of patients. Factors contributing to AD aggravation in pre-school children are the food factor (72.4%), contact with plant dust (43.1%) and stressful situations (17.2%). In patients with severe disease the rates of these factors were higher from 9 to 35%. The highest incidence of co-morbidity noted among children with severe AD was 2 times higher in patients with moderate severity. Conclusion. The AD severity in children of preschool age depends directly on the simultaneous presence of several major etiopathogenetic factors. In particular, the presence of food (72.47%) and pollen (54.5%) sensitization of the organism against the background of hereditary burden on allergic diseases (90.9%) leads to disease complication, which is 9% to 35% higher than in patients with moderate to mild severity.

Anti-inflammatory effect of galectin-1 in a murine model of atopic dermatitis.

Pharmacological treatment with rGal-1 reduces clinical signs of atopic dermatitis. Systemic treatment with rGal-1 inhibits eosinophil and mast cell influx in the skin of AD animals. rGal-1 reduced local eotaxin levels and systemic IL-17 levels. The inhibition of disease progression induced by rGal-1 was correlated with upregulation of phosphorylated ERK.

Clinical Signs, Staphylococcus and Atopic Eczema-Related Seromarkers

Childhood eczema or atopic dermatitis (AD) is a distressing disease associated with pruritus, sleep disturbance, impaired quality of life and Staphylococcus aureus isolation. The pathophysiology of AD is complex and various seromarkers of immunity are involved. We investigated if anti-staphylococcal enterotoxin IgE (anti-SE), selected seromarkers of T regulatory (Treg), T helper (Th) and antigen-presenting cells (APC) are associated with clinical signs of disease severity and quality of life. Disease severity was assessed with the Scoring Atopic Dermatitis (SCORAD) index, and quality of life with the Children’s Dermatology Life Quality Index (CDLQI) in AD patients ≤18 years old. Concentrations of anti-staphylococcus enterotoxin A and B immunoglobulin E (anti-SEA and anti-SEB), selected Treg/Th/APC chemokines, skin hydration and transepidermal water loss (TEWL) were measured in these patients. Forty patients with AD [median (interquartile range) age of 13.1 (7.9) years) were recruited. Backward stepwise linear regression (controlling for age, personal allergic rhinitis and asthma, and other blood markers) showed the serum anti-SEB level was positively associated with S. aureus and S. epidermidis isolations, objective SCORAD, clinical signs and CDLQI. TNF-α (a Th1 cytokine) was positively associated with objective SCORAD (B = 4.935, p = 0.010), TGF-β (a Treg cytokine) negatively with disease extent (B = −0.015, p = 0.001), IL-18 (an APC cytokine) positively with disease extent (B = 0.438, p = 0.001) and with TEWL (B = 0.040, p = 0.010), and IL-23 (an APC cytokine) negatively with disease extent (B = −2.812, p = 0.006) and positively with pruritus (B = 0.387, p = 0.007). Conclusions: Blood levels of anti-SEB, Th1, Treg and APC cytokines are correlated with various clinical signs of AD. AD is a systemic immunologic disease involving Staphylococcus aureus, cellular, humoral, cytokine and chemokine pathophysiology.

Western blot analysis of sera from dogs with suspected food allergy.

Food allergy is often suspected in dogs with clinical signs of atopic dermatitis. This diagnosis is confirmed with an elimination diet and a subsequent challenge with regular food. Laboratory tests for the diagnosis of food allergy in dogs are unreliable and/or technically difficult. Cyno-DIAL® is a Western blot method that might assist with the selection of an appropriate elimination diet. To evaluate the performance of Cyno-DIAL® for the selection of an elimination diet and diagnosis of food allergy. Thirty eight dogs with atopic dermatitis completed an elimination diet. Combining the results of the diet trials and the challenges, 14 dogs were classified as food allergic (FA), 22 as nonfood-allergic and two as ambiguous cases. Amongst all dogs and amongst dogs with a clinical diagnosis of FA, 3% and 7% (respectively) were positive to Royal Canin Anallergenic® , Vet-Concept Kanguru® or Vet-Concept Dog Sana® ; 8% and 7% to Hill's d/d Duck and Rice® ; 8% and 21% to Hill's z/d Ultra Allergen Free® ; 53% and 64% to Eukanuba Dermatosis FP® ; and 32% and 43% to a home-cooked diet of horse meat, potatoes and zucchini. The specificity and sensitivity of Cyno-DIAL® for diagnosing food allergy were 73% and 71%, respectively. Although Cyno-DIAL® was considered potentially useful for identifying appropriate foods for elimination diet trials, it cannot be recommended for the diagnosis of food allergy. The Cyno-DIAL® test performed better than some previously evaluated ELISA-based tests.

Measurement of transepidermal water loss (TEWL) in cats with experimental skin barrier dysfunction using a closed chamber system.

A closed chamber evaporimeter is suitable for measuring transepidermal water loss (TEWL) in cats because of the compact device size, tolerance to sudden movement and short measuring time. TEWL is a representative parameter for skin barrier dysfunction, which is one of the clinical signs of atopic dermatitis in humans and dogs. Measurement of feline TEWL has been reported, but applicability of this parameter has not been validated. The aims of this study were to determine if tape stripping is a valid experimental model in cats for studying TEWL and to determine if a closed chambered system is a suitable measurement tool for cats. Ten clinically normal cats. In order to evaluate variation of the measured values, TEWL was measured at the right and left side of the three clipped regions (axillae, lateral thigh and groin). Subsequently, TEWL was measured using sequential tape stripping of the stratum corneum as a model of acute barrier disruption. The variations between both sides of the three regions showed no significant difference. Sequential tape stripping was associated with increasing values for TEWL. Feline TEWL was shown to reflect changes in the skin barrier in an experimental model using a closed chamber system and has the potential for evaluating skin barrier function in cats with skin diseases.

Control of Recurrent Pyoderma with PYOspot® in an Atopic Dog

Recurrent pyoderma is not an uncommon complication of canine atopic dermatitis and the use of frequent courses of antibiotic for its control is of concern, related to the possible developing of resistances. This report describes a case where the use of a spot-on product PYOspot® avoids the recurrence of pyoderma in a dog with severe canine atopic dermatitis. A female French bulldog severely affected by canine atopic dermatitis was suffering from recurrent episodes of pyoderma, 5 in the last year. Pyoderma was manifested as bacterial folliculitis with alopecia and papule-crusted lesions and as intertrigo in facial folds and paws. The infection was controlled with courses of antibiotic lasting at least for 1 month, but it recurred once the treatment was stopped. The dog was in treatment with cyclosporine to control clinical signs of atopic dermatitis. The administration of a weekly treatment with a topical spot-on formulation containing a natural complex with antimicrobial properties, PYOspot ® , prevents pyoderma recurrence in this dog.

The Leaves of Broussonetia kazinoki Siebold Inhibit Atopic Dermatitis-Like Response on Mite Allergen-Treated Nc/Nga Mice.

Broussonetia kazinoki Siebold. (B. kazinoki) has long been used in the manufacture of paper in Asian countries. Although B. kazinoki leaves (BK) have been employed in dermatological therapy, use of BK has not been tested in patients with atopic dermatitis (AD). Using Nc/Nga mice, which are genetically predisposed to develop AD-like skin lesions, we confirmed the efficacy of BK in AD treatment. BK extract was applied topically to Dermatophagoides farinae-induced AD-like lesions in Nc/Nga mice, and the effects were assessed both clinically and by measuring skin thickness on the back and ears. We measured the effects of BK extract on plasma levels of IgE and IL-4. We also measured the ability of BK extract to inhibit the secretion of hTARC in HaCaT cells after stimulation by TNF-α and IFN-γ. We found that BK extract significantly reduced ear and dorsal skin thickness and the clinical signs of AD, as well as significantly down-regulating the plasma levels of IgE and IL-4 (p<0.01 for each comparison). Moreover, 500 μg/mL of BK extract inhibited hTARC secretion in HaCaT cells by activated TNF-α/IFN-γ by about 87%. These findings suggest that topical application of BK extract has excellent potential in the treatment of AD.

Effects of Lactobacillus rhamnosus on allergic march model by suppressing Th2, Th17, and TSLP responses via CD4(+)CD25(+)Foxp3(+) Tregs.

Allergic march (AM) is characterized by the progression of clinical signs of atopic dermatitis (AD) to allergic asthma or rhinitis, but its pathogenesis is not completely understood. We developed mouse model of AM with three 1-week exposures (separated by 2-week interval) to an OVA or saline (control) followed by OVA challenge. The development of AM was confirmed by phenotypes of AD and allergic asthma. Increases in IL-4, IL-17, and thymic stromal lymphopoietin (TSLP) responses were associated with the progression of AM, and these responses were suppressed by treatment with Lcr35. Moreover, Lcr35 treatment led to an increase in the number of CD4(+)CD25(+) Foxp3(+) regulatory T (Treg) cells in the mesenteric lymph nodes (MLNs) of AM mice. In conclusion, the oral application of Lcr35 prevented the development of AM in this model by suppressing Th2, Th17, and TSLP responses via a mechanism that may involve CD4(+)CD25(+)Foxp3(+) Tregs in MLNs.

Assessment of clinical signs of atopic dermatitis: A systematic review and recommendation

Clinical signs are a core outcome domain for atopic dermatitis (AD) trials. The current lack of standardization of outcome measures in AD trials hampers evidence-based communication. We sought to provide evidence-based recommendations for the measurement of clinical signs in AD trials and to inform the Harmonising Outcome Measures for Atopic Dermatitis Initiative. We conducted a systematic review on measurement properties of outcome measurements for clinical signs of AD. We systematically searched MEDLINE and Embase (until October 1, 2012) for validation studies on instruments measuring the clinical signs of AD. Grading of the truth, discrimination, and feasibility of scales; methodological study quality; and recommendations were based on predefined criteria. Sixteen eligible instruments were identified, of which 2 were best validated. The Eczema Area and Severity Index has adequate validity, responsiveness, internal consistency, intraobserver reliability, and intermediate interobserver reliability but unclear interpretability and feasibility. The Severity Scoring of Atopic Dermatitis Index (SCORAD) has adequate validity, responsiveness, interobserver reliability, and interpretability and unclear intraobserver reliability. Only the objective SCORAD (ie, the clinical signs domain of the SCORAD) is internally consistent. The Six Area, Six Sign Atopic Dermatitis Index severity score and Three Item Severity Score fulfill some quality criteria, but the performance in other required measurement properties is unclear. The Patient-oriented Eczema Measure is reliable and responsive but has inadequate content validity to assess clinical signs of AD. The remaining 11 scales have either (almost) not been validated or performed inadequately. The Eczema Area and Severity Index and SCORAD are the best instruments to assess the clinical signs of AD. The other 14 instruments identified are (currently) not recommended because of unclear or inadequate measurement properties.