Filaggrin Mutation Status and Prevention of Atopic Dermatitis with Maternal Probiotic Supplementation.

The World Allergy Organization recommends probiotics in the prevention of atopic dermatitis in high-risk populations. Mutations in the filaggrin gene (FLG) result in an increased risk of atopic dermatitis through disruption of the skin keratin layer. This exploratory study investigated whether the preventive effect of maternal probiotics was evident in children with and without FLG mutations. DNA was collected from children (n = 228) from the Probiotic in the Prevention of Allergy among Children in Trondheim (ProPACT) study. Samples were analysed for 3 common FLG mutations (R501X, R2447X, and 2282del4). Overall, 7% of children had heterozygous FLG mutations; each child had only one of the 3 mutations. Mutation status had no association with atopic dermatitis (RR = 1.1; 95% CI 0.5 to 2.3). The risk ratio (RR) for having atopic dermatitis following maternal probiotics was 0.6 (95% CI 0.4 to 0.9) and RR was similar if the child expressed an FLG mutation (RR = 0.6; 95% CI 0.1 to 4.1) or wildtype FLG (RR = 0.6; 95% CI 0.4 to 0.9). The preventive  effect of probiotics for atopic dermatitis was also evident in children without FLG mutation. Larger confirmatory studies are needed.

Which Clinical Measurement Tools for Atopic Dermatitis Severity Make the Most Sense in Clinical Practice?

Assessment of atopic dermatitis (AD) severity is essential for therapeutic decision making and monitoring treatment progress. However, there are a myriad of clinical measurement tools available, some of which are impractical for routine clinical use despite being recommended for clinical trials in AD. For measurement tools to be used in clinical practice, they should be valid, reliable, rapidly completed, and scored, and easily incorporated into existing clinic workflows. This narrative review addresses content, validity, and feasibility, and provides a simplified repertoire of assessments for clinical assessment of AD based on prior evidence and expert opinion. Tools that may be feasible for clinical practice include patient-reported outcomes (eg, dermatology life quality index, patient-oriented eczema measure, numerical rating scales for itch, pain, and sleep disturbance, AD Control Tool, and patient-reported global assessment), and clinician-reported outcomes (eg, body surface area and investigator's global assessment). AD is associated with variable clinical signs, symptoms, extent of lesions, longitudinal course, comorbidities, and impacts. Any single domain is insufficient to holistically characterize AD severity, select therapy, or monitor treatment response. A combination of these tools is recommended to balance completeness and feasibility.

A practical approach to caring for atopic dermatitis in children.

PURPOSE OF REVIEW: Atopic dermatitis is a chronic, systemic disease with primary cutaneous clinical manifestations and is commonly attributed to an exaggerated Th2 inflammatory response. Recent research regarding risk factors, prevention, clinical features, and management of atopic dermatitis will be reviewed. RECENT FINDINGS: In the last decade, advances have been made in identifying the factors that either confer increased risk for or protection from atopic dermatitis and associated atopy. Progress has also been made in the clinical management of this disease. Promising biomarkers and therapeutically informative characteristics of this disease have been identified in young children with and without the presence of eczema, but much has yet to be elucidated. Progress has also been made in clarifying the advantages and disadvantages of respective medical managements, including but not limited to topical corticosteroids, topical calcineurin inhibitors, phototherapy, systemic immunosuppressants, and targeted immunotherapy. Given that medical management may show variable efficacy in a child, an optimized skin care regimen is of utmost importance as well. SUMMARY: Atopic dermatitis is a challenging, chronic systemic disease that incurs significant morbidity in affected children. Although management options have been somewhat disappointing in years past, promising results have been observed in recent advances in targeted immunotherapy.

Concurrent Atopic Dermatitis and Psoriasis Successfully Treated With Dual Biologic Therapy.

Atopic dermatitis (AD) and psoriasis are chronic inflammatory skin conditions with clinical and histopathologic features that often overlap, representing an underlying immunopathological spectrum of disease that can complicate the proper diagnosis and treatment of both conditions. We report the case of a patient with longstanding concurrent, treatment-resistant AD and psoriasis who was successfully treated with dual biologic therapy with dupilumab and guselkumab. Our case highlights the importance of considering coexisting AD and psoriasis in patients with treatment-resistant disease and the utility of dual biologic therapy. We also review an established but rare incidence of overlap between AD and psoriasis and highlight diagnostic challenges and the importance of assessing patients comprehensively. Our case also demonstrates the utility of patch testing and tissue diagnosis in patients with concurrent AD and psoriasis, as well as the importance of considering both diagnostic testing and clinical response in clinical decision-making.

Expert opinion on management of moderate-to-severe atopic dermatitis in Qatar.

Atopic dermatitis (AD), a chronic-relapsing inflammatory skin disorder, manifests with intense itching and eczematous lesions impairing quality of life. A heterogeneous population, and regional clinical practices for treating AD warrant the development of guidelines in Qatar. Therefore, guidelines for the management of moderate-to-severe AD in Qatar have been developed and discussed. Experts, including dermatologists and immunologists, used the Delphi technique for developing guidelines. Consensus was defined as ≥75% agreement or disagreement. AD is highly prevalent in primary and tertiary dermatology centers. AD-associated foot eczema and psoriasiform eczema are more frequent in Qatar than in Europe or USA. SCORing Atopic Dermatitis Index quantifies disease severity and itch. Dermatology Life Quality Index assesses the quality of life. Atopic Dermatitis Control Tool assesses long-term disease control. Moderate-severe AD benefits from new topicals like Janus-kinase-inhibitors or PDE4-inhibitors combined with phototherapy. Currently approved systemic agents are dupilumab, baricitinib, abrocitinib, and upadacitinib. New anti-IL-13 and anti-IL-31 therapies will soon be available. Patient education, allergy testing, and comorbidity consideration are critical in the management of AD. The expert panel established a comprehensive and pragmatic approach to managing moderate-to-severe AD, thereby assisting clinical decision-making for healthcare professionals in Qatar.

Update on Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder with a lifetime prevalence of up to 20% which can occur at any age but is most common among children. There is a significant burden of pediatric AD in the primary care setting; thus, the ability to recognize and manage AD is of utmost importance to pediatricians. Treatment of AD requires a multifaceted approach based on a patient's severity including behavioral modifications, topical and systemic pharmacologic therapies, and phototherapy.

Real-Life Experience of Tralokinumab for the Treatment of Adult Patients with Severe Atopic Dermatitis: A Multicentric Prospective Study.

BACKGROUND: Tralokinumab, the first fully human monoclonal antibody that binds specifically to interleukin-13, was safe and effective for treating atopic dermatitis (AD) in clinical trials, but real-life experience is still limited. OBJECTIVES: The objective of this study was to evaluate the effectiveness and safety of tralokinumab in severe AD in a real-life multicenter prospective cohort. METHODS: Adult patients with severe AD were enrolled between January 2022 and July 2022 and received tralokinumab subcutaneously for 16 weeks. Objective and subjective scores were collected at baseline, weeks 6 and 16. Adverse events were reported throughout the study. RESULTS: Twenty-one patients were included. An improvement of at least 75% on the Eczema Area and Severity Index (EASI 75) was achieved in 66.7% of patients at week 16. The median objective and subjective scores at week 16 were significantly (p < 0.001) lower than those at baseline. Combination with cyclosporine was sometimes necessary at the beginning of treatment, and addition of upadacitinib was required for some patients with very severe disease during the treatment. The most frequent adverse events were flares of eczema (23.8%) and reactions at injection site (19.0%). No cases of conjunctivitis were reported. Four patients (19.0%) discontinued treatment. CONCLUSIONS: Tralokinumab is an effective first-line biotherapy for severe AD. However, therapeutic response may be progressive. Safety data were reassuring. Atopic dermatitis flares or reactions at the injection site may lead to discontinuation of treatment. A history of conjunctivitis on dupilumab is not a contraindication to the initiation of tralokinumab.

Combined application of dupilumab and mite allergen-specific immunotherapy in children with moderate to severe atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease that manifests in skin dryness, severe itching, and eczema, and can significantly impact a patient's quality of life. Current treatment regimens do not prevent the recurrence of the disease and are associated with adverse effects. Here, we report two cases of moderate-to-severe AD in children that were treated with dupilumab, a dual inhibitor of IL-4 and IL-13 signaling, in combination with mite allergen-specific immunotherapy. CASE SUMMARY: Both patients presented with the diagnosis of AD that was not adequately controlled by the conventional treatment regimen, including topical corticosteroids (TCS), topical calcineurin inhibitors, emollients, and the traditional Chinese medicine treatments. In both patients, AD-associated skin irritation impacted the quality of life, disturbed sleep patterns, and caused stress and anxiety.Patients received treatment with dupilumab and mite allergen-specific immunotherapy in addition to the baseline treatment regimen of external glucocorticoids (TCS) and oral antihistamines. Nine months after beginning of treatment, clinical symptoms, signs, medication scores, and evaluation scale scores of both children significantly improved, and the treatment was associated with an overall good tolerance. CONCLUSION: A combination of dupilumab and mite allergen-specific immunotherapy in addition to the standard anti-AD treatment improves clinical symptoms and is not associated with increased incidence of adverse effects.

Guidelines for the Management of Atopic Dermatitis in Children: A Systematic Review.

INTRODUCTION: Numerous guidelines have been published for atopic dermatitis management in children in recent years. To date, the quality of the newest guidelines has not been appraised. This study aimed to identify and evaluate guidelines for the management of atopic dermatitis in children. METHODS: We reviewed the literature retrieved from PubMed, Web of Science, Ovid, ScienceDirect, Embase, China National Knowledge Infrastructure, WanFang Data, and guidelines websites. Search period from January 1, 2016, to December 31, 2021. The following keywords were used for searching: "atopic dermatitis," "atopic eczema," "eczema," "guideline," and "consensus." The quality of the guidelines was assessed by two assessors using the Appraisal of Guidelines for Research & Evaluation II (AGREE II) instrument independently, and domain scores >60% were considered to have sufficient quality. The guideline recommendations were reviewed. RESULTS: Nineteen guidelines were included in the study. Three guidelines had a graded A level, which was recommended for use in practice. Eleven guidelines had a graded B level, which was recommended for use in revision. The remaining five guidelines were rated with C level, which was not recommended. The average score of six domains of AGREE II was 64.76%, 48.53%, 42.35%, 73.83%, 32.23%, and 70.17%, respectively. A consistency test showed an intraclass correlation coefficient range of 0.497 (95% CI: 0.105, 0.705) to 0.970 (95% CI: 0.93, 0.987) based on the two assessors' test results for the guidelines. CONCLUSIONS: Most guidelines were recommended for use with revision. No significant changes were observed in the primary management of atopic dermatitis in children compared to previous evidence. New biological agents and complementary alternative medicine are increasingly available, but the evidence for the treatment of atopic dermatitis in children is still limited.

The effect of fatty acids, vitamins, and minerals on pediatric atopic dermatitis: A systematic review.

BACKGROUND: A body of research has examined the role of fatty acid (FA), vitamin, and mineral supplementation as adjunctive treatment for atopic dermatitis (AD); however, results are conflicting and concrete recommendations are lacking. The objective of this study is to highlight the role of these nutrients in alleviating AD severity and provide the clinician with consolidated information that can be used to make recommendations to the pediatric patient and caretaker, where this topic is of high interest. METHODS: A review of the PubMed and Embase databases was conducted to identify and qualitatively analyze all randomized controlled trials, systematic reviews, and meta-analyses conducted within the last 21 years regarding use of these nutrients to alleviate symptoms of AD. Inclusion criteria include AD diagnosis, non-infant age groups, and AD severity outcomes; exclusion criteria include preventative studies, predominantly maternal or infant demographics, or nonclinical outcomes. RESULTS: Sixty-nine studies were included. Evidence regarding FA supplementation is inconclusive; however, targeting an ideal omega-3:omega-6 FA ratio may play a small role in alleviating AD symptoms. Studies results regarding vitamin/mineral supplementation are inconsistent and supplementation should not be advised unless the patient has a documented deficiency. CONCLUSION: Pediatric AD patients should lead a healthy lifestyle with an emphasis on consumption of wholesome foods. Nutritional supplementation can play a role in improving AD symptoms; however, this should be evaluated on a case-by-case basis. Limitations include heterogeneity of studies.

The impact of vitamin D supplementation on serum cathelicidin levels and the clinical course of atopic dermatitis in children.

BACKGROUND: Cathelicidin has been correlated with the pathophysiology of atopic dermatitis (AD). An indirect correlation of vitamin D with the course of the disease has already been reported as it directly affects the levels of cathelicidin. The purpose of the present article is to investigate the impact of vitamin D supplementation on the course of AD. METHODS: We conducted a prospective observational study. The severity of AD was assessed with the clinical tool SCORAD (SCORing Atopic Dermatitis) which is developed by the European Task Force on AD. RESULTS: Fifty children with AD were enrolled and stratified in two groups based on the severity of SCORAD. Children with severe AD (SCORAD Index >40) received higher doses of vitamin D in order to sufficiently reduce the disease (comparable SCORAD Index for children with mild atopic dermatitis). While the baseline SCORAD differed statistically significant level between the two groups of children with AD (P<0.001) this difference disappeared at 20 (P=0.649) days and remained statistically insignificant both at 45 days (P=0.610), and at the end of the administration of treatment (P=0.474). This effect was based on a significant downregulation of the severity of symptoms in the group of children that received 2400 IU of vitamin D. CONCLUSIONS: The findings of our study suggest that vitamin D may be accurately used in current clinical practice for the management of AD. However, the recommended dose should be titrated taking in mind the severity of the disease.

Effect of moderate to severe atopic dermatitis on the prognosis of egg allergy resolution

BACKGROUND: Few studies have examined the effect of atopic dermatitis (AD) on the resolution of food allergies in Asia, and the predictors of egg allergy resolution are not yet well defined. OBJECTIVE: We evaluated whether AD severity could predict the resolution of egg allergy. METHODS: This retrospective cohort study included infants under 24 months of age diagnosed with IgE-mediated egg white allergy. We included subjects who completed a 60-month follow-up. Open oral food challenges (OFCs) and serologic tests were performed at the time of initial diagnosis and at 36 ± 3 and 60 ± 3 months. RESULTS: We analyzed 68 patients (39 boys and 29 girls). OFCs were performed in 88.2% of the patients. The egg allergy remission rates were 23.5% and 47.1% by 3 and by 5 years of age, respectively. Persistent egg allergy was significantly associated with moderate to severe AD and house dust mite sensitization. Kaplan-Meier curve analysis revealed that patients with moderate to severe AD had higher persistent egg allergy rates than patients with no and mild AD (p = 0.012). Multivariable analysis identified moderate to severe AD as strongly associated with persistent egg allergy (p = 0.001). CONCLUSIONS: In this study, 47.1% of infants had resolved egg white allergies at 60 months. Moderate to severe AD may be a practical and important prognostic factor for persistent egg allergy in clinical settings.

Treatment options for moderate to severe atopic dermatitis.

Background: The treatment of chronic refractory moderate-to-severe atopic dermatitis (AD) has traditionally relied on broad-spectrum systemic anti-inflammatory agents. With the introduction of biologics and Janus kinase inhibitors (Jakinib), the step management of moderate-to-severe AD is rapidly changing; however, guidelines have yet to provide formal recommendations for how to best incorporate these agents into the treatment plan. Objective: To summarize the updated evidence-based medical treatment for AD, including a proposed position for biologics and Jakinibs in the treatment algorithm. Methods: A literature search of several medical literature data bases for guidelines, position papers, systematic reviews, and clinical trials from 2012 to 2022 on the treatment of moderate-to-severe AD was conducted to prepare this narrative review. Results: Emollients and topical corticosteroids are the mainstay for treating acute flares and for maintaining chronic control. Second-line topical agents include calcineurin inhibitors, e.g., tacrolimus and pimecrolimus; crisaborole; and ruxolitinib. For acute flares, cyclosporine is preferred over systemic corticosteroids. For chronic treatment, phototherapy should be considered before systemic anti-inflammatory agents. Of the traditional anti-inflammatory agents, cyclosporine is the first-line choice, with methotrexate and azathioprine equal secondary choices. Although abrocitinib may have better efficacy then dupilumab based on indirect comparisons, abrocitinib requires closer monitoring for adverse events. Based on package labeling, Jakinibs, e.g., abrocitinib and upadacitinib, should be used only after failure with other systemic agents, including biologics (e.g., dupilumab and tralokinumab). Biologics and Jakinibs should be considered before the traditional systemic anti-inflammatory agents. Conclusion: Clinicians should consider a modified step management for AD as they await the development of national and international guideline recommendations for how best to position the biologics and Jakinibs into the AD treatment algorithm.

Efficacy and Safety of Fig (Ficus carica L.) Leaf Tea in Adults with Mild Atopic Dermatitis: A Double-Blind, Randomized, Placebo-Controlled Preliminary Trial.

Atopic dermatitis (AD) is a chronic, recurrent pruritic skin disease with repeated remissions and exacerbations. Various factors, such as allergies, skin conditions and lifestyle, combine to cause AD, making it difficult to cure completely. Although AD symptoms are suppressed with medications, this is a long-term effort and burden on patients. Thus, safer drugs and alternatives are needed. We previously found that consumption of tea prepared from fig (Ficus carica L.) leaves alleviated allergy and AD symptoms in cultured cells and animals. Therefore, here, we conducted a double-blind, randomized, controlled study in patients with mild AD to evaluate the safety and AD-relieving effects of prolonged consumption of fig leaf tea. Positive effects of fig leaf tea consumption were confirmed in 14 of 15 participants. Eczema Area and Severity Index values were significantly lowered in the fig leaf tea-treated group than in the placebo-treated group. The effect weakened 4 weeks after the end of the intervention, suggesting that continued intake of fig leaf tea was effective. Further assessments confirmed the safety of fig leaf tea consumption and revealed no variations that might pose a health hazard. Therefore, we postulate that fig leaf tea is a natural and safe therapeutic option for AD.

Dupilumab dose spacing after initial successful treatment or adverse events in adult patients with atopic dermatitis: A retrospective analysis.

Strategies on long-term management of patients affected by atopic dermatitis (AD) undergoing treatment with dupilumab achieving good clinical response (GCR) or experiencing dupilumab-related adverse events (AEs) are scant. Data of patients who implemented longer than scheduled dupilumab dosing interval due to GCR (at least 52 weeks of treatment and controlled AD activity [Eczema Area Severity Index ≤7 and Dermatology Life Quality Index ≤5 for at least 6 months]) or AEs (dupilumab-related and treatment-resistant conjunctivitis) were retrospectively collected. Dupilumab was tapered to Q3W or Q4W based on physician-patient shared decision. At baseline (T0) and each follow-up (week 16 [T1] and week 32 [T2]) disease severity was assessed. A total of 59 patients implemented longer than scheduled dosing interval (44 GCR, 15 AEs). Among these, 50 (35 GCR and 15 conjunctivitis) patients switched to 300 mg Q3W, while nine GCR subjects to Q4W. In the GCR group Q3W, 34 and 31 patients maintained clinical response at T1 and T2, whereas eight and seven Q4W subjects maintained clinical response at the same timepoints, respectively. No significant differences in AD severity were observed between T1 and T2 in both groups. Contrariwise, one Q3W and one Q4W patients at T1, and three Q3W and one Q4W subjects at T2, returned to dupilumab labeled dosage due to AD worsening. In conjunctivitis group, dupilumab Q3W was maintained in eight and four patients at T1 and T2, respectively. Three patients at T1 and three at T2 subjects returned to the labeled interval due to conjunctivitis remission. Four patients at T1 and four subjects at T2 interrupted dupilumab due to the persistence of conjunctivitis. A longer dupilumab dosing interval may be a valuable option in patients with a GCR and may be a useful strategy to reduce treatment-related conjunctivitis, also with pharmacoeconomic benefit.

Severe Protein Loss in a 6-month-old Exclusively Breastfed Infant with Atopic Dermatitis.

Protein loss is often the result of kidney or intestinal disease (protein-losing enteropathy) and can cause a number of serious, potentially life-threatening complications such as hypotension, thrombocytosis, electrolyte imbalance, and cerebellar ischemia. Recent research suggests an association between extremely severe atopic dermatitis (AD) and allergic enteropathy. An exclusively breastfed 6-month-old infant was admitted to our institution due to failure to thrive, electrolyte imbalance, and severe AD (SCORing Atopic Dermatitis; SCORAD 40). On admission, the infant was in poor general condition, dehydrated, malnourished (bodyweight 4870 g, -3.98 z-score), with exudative erythematous morphs scattered throughout the body. Initial laboratory results showed microcytic hypochromic anemia, hypoalbuminemia, hypogammaglobinemia, thrombocytosis, hyponatremia, high values of total immunoglobulin E (IgE), and eosinophilia. Polysensitization to a number of nutritional and inhalation allergens was demonstrated, and an exclusive amino acid-based formula has been introduced into the diet. During the hospital course, the patient developed superficial thrombophlebitis and methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. Eosinophilia was found in a small intestine biopsy sample. Due to severe hypogammaglobulinemia, skin infections, and bacteremia, the differential diagnosis included primary immune deficiency (STAT3 deficiency, DOCK8 deficiency, PGM3 deficiency, IPEX), but all available immunological tests were unremarkable. Exclusive amino acid-based formula diet was continued in the infant, with topical corticosteroids under wet-dressing therapy and intravenous immunoglobulin replacement therapy. With the gradual improvement of the general condition, the introduction of solid foods was started according to the findings of allergy testing. At 17 months of age, the patient gained weight and his skin status has been improving, although frequent use of topical corticosteroids was necessary. There were no infections, no anemia or thrombocytosis, and albumin and immunoglobulin supplementation were no longer required. The main mechanism of protein loss in infants with extremely severe atopic dermatitis is probably due to damaged skin, and partially due to the eosinophilic inflammation of the small intestine. Immunoglobulin loss, potentiated by physiological or transient hypogammaglobulinemia in infants, poses a very high risk for severe, potentially life-threatening infections.

The efficacy and safety of Longmu Tang granule for the treatment of atopic dermatitis: study protocol for a single-centred, double-blinded, randomised, placebo-controlled trial.

BACKGROUND: Atopic dermatitis (AD) is a chronic relapsing skin disease that has long-term physical and mental health impacts on children with this condition. Current treatments mainly include anti-inflammatory, antibacterial, and anti-allergic interventions, systemic therapy, and recently emerging target-focused agents. However, these treatments have limited effectiveness and unwanted side effects. The use of traditional Chinese medicine (TCM) in the treatment of AD has a long history, with promising efficacies, low toxicity, and improvements in the quality of life of patients with AD. Longmu Tang granule, a TCM, has been used to effectively treat AD since 2008 through doctors' prescriptions. To scientifically evaluate the clinical efficacy and safety of Longmu Tang granule, we proposed to launch a single-centred, double-blinded, randomised, placebo-controlled trial. METHODS: In this single-centred, double-blinded, randomised, placebo-controlled clinical trial conducted at Xiyuan Hospital of China Academy of Chinese Medical Sciences, a total of 60 participants will be randomly assigned (1:1) to receive the Longmu Tang granule or placebo granule for 8 weeks. The primary outcome will be evaluated using the index of Scoring Atopic Dermatitis. The secondary outcomes will be evaluated using the Children's Dermatology Life Quality Index and the number cancellation test. The mechanistic evidence will be the serum levels of inflammatory cytokines, including immunoglobulin E, tumour necrosis factor-α, interleukin-1, and interleukin-6. DISCUSSION: The results of this trial will provide evidence of the efficacy and safety of the Longmu Tang granule and prove its anti-inflammatory action in patients with AD. TRIAL REGISTRATION: Chinese Clinical Trial Registry Chictr.org ID: ChiCTR2100041591 . Registered on 1 January 2021.

Efficacy and safety profile of antioxidants in the treatment of atopic dermatitis: A systematic review and meta-analysis of randomized controlled trials.

The use of antioxidants in atopic dermatitis (AD) is controversial. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of antioxidants therapy in AD. Randomized clinical trials were identified from Medline, Embase, and Cochrane library. Changes from baseline in severity and itch score were extracted from individual studies and pooled using random-effects. Eighteen trials including 763 AD patients were eligible. Overall, antioxidants were associated with statistically significant reductions in diseases severity (p < 0.0001), but not with itch score (p = 0.59). No serious adverse events were recorded. Subgroup analyses revealed that antioxidants were associated with a significant reduction in severity score regardless of disease severity at baseline and treatment duration (p < 0.05). However, antioxidants had additional benefit only in children (p = 0.02) but not in adults (p = 0.30). Oral supplementation with vitamin D, combined vitamins D and E, combined vitamins A, D and E and topical vitamin B12 was associated with significantly lower severity score (p < 0.05). There was significant heterogeneity between studies (I2  = 50%; p = 0.003). The effect estimates did not change statistically after excluding sources of study heterogeneity. This meta-analysis suggests that antioxidants may be a safe and effective treatment for AD patients, especially when supplemented with oral vitamin D and topical vitamin B12 , as well as in pediatric patients.