Atopic dermatitis

Atopic Dermatitis: Current Innovations and Future Trends for Next 5 Years

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Introduction

Atopic dermatitis (AD) is a prevalent, persistent skin condition characterized by intense itching and inflammation (1). Globally, it impacts about 20% of children and 2–8% of adults, often with a personal or family history of AD (1).  In a systematic review conducted in June 2019, it was determined that the prevalence of AD is on the rise worldwide, with a slightly higher incidence observed in females (0.6–24.3%) compared to males (0.8–17.6%) (1). Hence, global treatment is imperative and essential for AD (1). Treatment choices are primarily determined by the severity of this disease (1). For mild-to-moderate cases, conventional options include topical corticosteroids (TCSs), topical calcineurin inhibitors (TCIs), and, in selected cases, ultraviolet radiation therapy (1). Moderate-to-severe instances may necessitate systemic immunosuppression using a short course of systemic corticosteroids or cyclosporine; alternatively, methotrexate, azathioprine, or mycophenolic acid may be prescribed (1). A recent addition to the therapeutic arsenal is the monoclonal antibody, dupilumab, which has demonstrated exceptional efficacy in managing both clinical signs and symptoms associated with AD (1).

This article delves into the current emerging treatment approaches for AD and anticipates the evolving landscape over the next 5 years (1,2).

Current emerging treatment for AD

 Table 1 showcases a range of emerging therapies with a promising profile in terms of clinical efficacy and safety for treating AD (1).

Table 1: Emerging therapies for AD (1)

Expected AD Treatment in Next 5 Years

Over the next 5 years, the treatment landscape for AD is expected to undergo significant changes, driven by the emergence of novel therapies and a shift towards more targeted and holistic approaches (2). These detailed figures are illustrated in figure 1 below (2).

Lebrikizumab plus topical steroids safe, effective in atopic dermatitis treatment

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Combination lebrikizumab and topical corticosteroids outperformed topical corticosteroids alone in the treatment of atopic dermatitis in adolescents and adults, according to a phase 3 study.

“Currently, emollients and topical corticosteroids (TCS) are mainstay treatments for mild AD. In moderate to severe AD, the addition of systemic therapy and/or phototherapy is recommended,” Eric L. Simpson, MD, MCR, Frances J. Storrs Medical Dermatology Professor at Oregon Health and Science University and principal investigator of the ADhere trial, and colleagues wrote. “Due to the heterogeneity of AD, there remains a need to provide additional therapeutic options for long-term management.”

Dermatitis itch 3
Combination lebrikizumab and topical corticosteroids outperformed topical corticosteroids alone in the treatment of atopic dermatitis in adolescents and adults.

The 16-week, double-blind, placebo-controlled, multicenter, phase 3 ADhere trial analyzed the efficacy and safety of lebrikizumab, a novel monoclonal antibody that targets and neutralizes interleukin-13 signaling, in combination with low- to mid-potency TCS for the treatment of AD in adolescents and adults. These results, published in JAMA Dermatology, follow an Eli Lilly press release from April 2022.

In the study, a total of 211 patients (median age, 37.2 years; 48.8% female) were randomly assigned to receive 500 mg of subcutaneous lebrikizumab at baseline and week 2 followed by 250 mg every 2 weeks plus TCS or placebo plus TCS for 16 weeks.

By week 16, results showed 41.2% of lebrikizumab plus TCS-treated patients achieved the primary endpoint of a 0 or 1 IGA score compared with 22.1% of the placebo group (P = .01). Additionally, 69.5% of patients treated with lebrikizumab plus TCS achieved the key secondary endpoint of EASI 75 compared with 42.2% of the placebo group (P < .001).

Safety data demonstrated findings consistent with previously reported AD trials. Most treatment-related adverse events were not considered serious and were mild or moderate in severity, according to the study, and included conjunctivitis, headache, hypertension, injection site reactions and herpes infection. Serious adverse events were reported by two patients in the lebrikizumab plus TCS group and one patient in the placebo group.

“Treatment with [lebrikizumab plus TCS vs. placebo plus TCS] achieved statistically significant improvements in the signs and symptoms of moderate to severe AD in adolescents and adults,” Simpson and colleagues wrote. “The [lebrikizumab plus TCS] group had a benefit to risk profile consistent with prior lebrikizumab AD studies. Taken together, the efficacy and safety data reported herein suggest that [lebrikizumab plus TCS] may be an effective treatment option for adult and adolescent patients with moderate to severe AD.”

Lebrikizumab effective against moderate-to-severe atopic dermatitis, trials find

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Key takeaways:

  • The whole monoclonal antibody lebrikizumab was effective in a pair of trials against atopic dermatitis in children and adults.
  • The goal is FDA approval by the end of 2023.

Two phase 3 trials found that lebrikizumab was effective against moderate-to-severe atopic dermatitis in adolescents and adults, researchers reported in The New England Journal of Medicine.

“Lebrikizumab is a whole monoclonal antibody that targets interleukin-13, which has been shown to be important in the pathogenesis of atopic dermatitis,” Jonathan I. Silverberg, MD, PhD, MPH, director of clinical research and an associate professor of dermatology at the George Washington University School of Medicine and Health Sciences, told Healio.

IDC0323Silverberg_Graphic_01_WEB

Silverberg and colleagues conducted a pair of randomized, double-blind, placebo-controlled phase 3 trials of lebrikizumab administered subcutaneously every 2 weeks to adolescents aged 12 to 17 years and adults aged 18 year or older with moderate-to-severe atopic dermatitis.

Both trials included a 16-week induction period and a 36-week maintenance period. The results reported in the journal included outcomes only for the 16-week induction period.

The researchers randomly assigned participants in a 2:1 ratio to receive a 250 mg dose of either lebrikizumab or a placebo, administered under the skin every 2 weeks throughout the induction period, with a loading dose of 500 mg given at baseline and week 2.

Silverberg and colleagues measured outcomes using an Investigator’s Global Assessment score ranging from 0 to 4. The primary outcome was a score of 0 or 1 — which indicates “clear or almost clear skin,” they wrote — with a score reduction of at least 2 points from baseline at week 16, which they noted would indicate an improvement.

In the first trial, 43.1% of 283 subjects in the lebrikizumab group met the primary outcome compared with 12.7% of 141 patients in the control group, the researchers reported. In the second trial, 33.2% of 281 patients in the lebrikizumab group met the primary outcome vs. 10.8% of 146 patients in the control group.

“There were many, many outcome measures that were assessed, and it almost didn’t matter. All of them showed great improvement with lebrikizumab treatment,” Silverberg said. “We were certainly very optimistic already based on the last few studies, and quite fortunately, the results have delivered, I think, as well or even better than anyone expected.”

“When we see this kind of reproducible high level of efficacy with a collective interleukin-13 blocker, and compare that with other therapies that are out there, it indicates that this mechanism, indeed, is highly effective and is sufficient, essentially to achieve good results,” Silverberg said.

He said they are “optimistic” that lebrikizumab will be authorized by the end of the year.

“Our hope is that the FDA will approve lebrikizumab before the end of 2023,” Silverberg said.

Wearable digital technology measures atopic dermatitis itch while sleeping

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The use of wearable digital health monitors that measure itch and scratch during sleep appeared useful for patients with atopic dermatitis, according to study results.

“If a person knows how much itching they’re having at night, then they can also share that with their physician or other health care practitioner, informing them of the status of their atopic dermatitis,” Donna D. (De De) Gardner, DrPH, RRT, FCCP, FAARC, director of research and evaluation at Allergy & Asthma Network, told Healio.

Man sleeping with Apple Watch
Though most patients agreed that the information provided by the technology was useful, few said they would discuss the data with their physicians. Source: Adobe Stock

For the study, presented at the American College of Allergy, Asthma & Immunology Annual Scientific Meeting, researchers recruited respondents from a dermatology office and the Allergy & Asthma Network community via email between December 2020 and April 2021. Most of the participants were white women aged 35 to 50 years, Gardner said.

Participants needed to have an Apple iPhone and Apple Watch; those without the watch received one to use during the study.

Next, participants downloaded the DermaTrack (Embleema) application onto their iPhone to measure vibrations and movement in the skin and record when users scratch themselves.

The participants also completed the Dermatology Life Quality Index (DLQI) and a demographic survey, in addition to daily surveys and a final satisfaction survey.

Of the 81 participants who completed the DLQI, 53 said that their AD determined what clothes they were going to wear each day, 41 said their social activities depended on their AD status, 28 said they were hesitant to have sex with their partner because of their AD and 61 said they were embarrassed or overly conscious of their AD.

“And then 73, almost all of the participants, said that their skin was itchy, sore and painful,” said Gardner. “So atopic dermatitis does, as we know, impact quality of life.”

Overall, 79% of the participants agreed that AD had a moderate to large effect on their life.

For 7 nights, the participants wore the Apple Watch while they slept.

Data from the app showed patients experienced a maximum of 32 minutes of itching a night, indicating scratch from AD impacts sleep as well, Gardner said.

“If you could imagine itching constantly for 32 minutes, that’s painful and is going to interrupt your sleep,” Gardner said. “These people are not sleeping at night, and their quality of life is poor.”

The app’s dashboard then let participants review these data and share it with their physicians. Although 89% of the participants agreed that the information was useful, only 53% said it would enable them to better discuss their AD with their physician, and even fewer said they would do so.

“The sad thing is that even though people were informed, only a third of them said they would actually have the conversation,” Gardner said. “That tells you that they are hesitant to have the conversation with their health care provider about the status of their atopic dermatitis.”

Nickel allergic contact dermatitis

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A 41-year-old man presented to the dermatology clinic with a 1-month history of erythematous, pruritic papules on the abdomen. The periumbilical skin had 2 symmetric erythematous plaques with overlying scaly, hyperkeratotic tissue and eczematous papules (Figure 1A). The lesions were confined to the skin in contact with a metallic belt buckle purchased 3 months before. Positive patch test (++) for nickel sulfate (5.0%) in petroleum confirmed contact dermatitis to nickel (Appendix 1, available at www.cmaj.ca/lookup/doi/10.1503/cmaj.220260/tab-related-content). We prescribed a 7-day course of mometasone furoate (0.1%) cream, which led to a substantial improvement (Figure 1B). We recommended that the patient avoid future contact with nickel-containing accessories and use brass or plastic fasteners, belts and buckles instead.

Figure 1:

Nickel allergic contact dermatitis: (A) Periumbilical skin of a 41-year-old man with 2 erythematous plaques with overlying pruritic and eczematous papules. (B) A marked improvement was observed after 1 week of using a topical corticosteroid.

A meta-analysis of 20 000 people from the general population who were patch tested confirmed a 20% prevalence of contact allergy, with nickel being the most common allergen (11.4%).1 Prevalence is higher in women and people with atopic disorders.2 Nickel allergic contact dermatitis results from a type IV cutaneous hypersensitivity reaction, although symptoms can occur within the first 30 minutes of exposure.3 Prolonged contact with the skin, sweat and friction can induce subclinical maceration and release of nickel into the skin.

Differential diagnoses include scabies, impetigo, psoriasis, inflammatory dermatoses, mycosis fungoides, tinea corporis, atopic dermatitis and fixed drug eruptions.4 Presentation varies from mild dermatitis with pruritus, deep erythema with oozing and papulation, to a systemic reaction with generalized idiopathic hypersensitivity. Patch testing can confirm the etiologic agent, and skin biopsy may help if the diagnosis is uncertain. Standard treatment is to remove the source object and prescribe topical corticosteroids.5 Calcineurin inhibitors (i.e., tacrolimus) can be considered for steroid-resistant cases, and oral steroids or antihistamines to aid in symptom resolution.

Clinical images are chosen because they are particularly intriguing, classic or dramatic. Submissions of clear, appropriately labelled high-resolution images must be accompanied by a figure caption. A brief explanation (300 words maximum) of the educational importance of the images with minimal references is required. The patient’s written consent for publication must be obtained before submission.

Atopic dermatitis disease burden multidimensional

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Atopic dermatitis disease burden is affected by severity and time spent managing the disease, according to a study.

“Our findings highlight that AD is much more than a rash, and has a myriad of negative impacts on patients’ lives, especially those with moderate to severe disease,” Wendy Smith Begolka, MBS, senior vice president of scientific and clinical affairs at the National Eczema Association (NEA) and one of the study’s authors, told Healio. “Second, each individual affected by AD has a unique lived experience. Physical, emotional, social and other elements can variably contribute over time to the patient’s perspective of disease burden.”

Woman in a yellow short scratches her arm.
Atopic dermatitis disease burden is affected by severity and time spent managing the disease.

Begolka and colleagues conducted an analysis of data collected from a 32-item survey sent through patient advocacy groups, social media and clinicians. More than 1,000 patients with AD responded to the survey, which asked for a rating of overall impact of AD and specific elements of disease burden on an ordinal scale of 1 (no impact) to 5 (significant impact).

Of 1,065 patients, the majority reported having moderate AD (n = 467; 45%) or severe AD (n = 198; 28%), with 845 (80%) reporting their disease was severe when at its worse.

Thirty-two (3%) respondents said their AD had no overall disease burden in the preceding month, while 194 (18%) reported a low impact, 295 (28%) reported a moderate impact and 228 (21%) reported a high impact. Also, 316 (30%) said their AD had a significant impact on their lives.

Higher AD severity was subsequently associated with more disease burden compared with those with mild disease, according to a multivariable proportional odds model.

Additionally, mood changes were also associated with AD severity.

“Overall AD disease burden is not driven by any single disease or quality of life impact, underscoring its complex heterogeneity,” Smith Begolka said. “There is a significant negative effect of AD on the lives of adult patients. … The burden of AD is multidimensional and can be uniquely experienced by affected individuals.”

FDA approves Dupixent for atopic dermatitis in young children

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The FDA has extended the approval of Dupixent to include children aged 6 months to 5 years with moderate to severe atopic dermatitis, Regeneron Pharmaceuticals and Sanofi announced in a press release.

“We’ve had Dupixent now for the past few years, but there are many children who are under 6 who are also suffering from atopic dermatitis,” Amy S. Paller, MD, primary investigator at Northwestern University’s Skin Disease Research Center, told Healio. “It’s been great to have some new studies come out that show it’s just as efficacious and that the safety is the same.”

Dermatitis child
The FDA has extended the approval of Dupixent to include children aged 6 months to 5 years with moderate to severe atopic dermatitis. 

The approval was based on phase 3 data that found 200 mg or 300 mg of Dupixent (dupilumab), based on body weight, plus low-potency topical corticosteroids resulted in clear or almost clear skin in 28% of patients, compared with 4% of those treated with placebo. Overall disease severity improved by at least 75% in 53% of patients, compared with 11% of placebo-treated patients and a clinically meaningful reduction in itch was achieved in 48% of those treated with Dupixent, compared with 9% of those treated with placebo.

Amy S. Paller

Dupixent is the first biologic approved to treat atopic dermatitis in individuals from infancy to adulthood.

“Until today, treatment options in the U.S. for infants and children under the age of 6 suffering from moderate to severe atopic dermatitis have been limited to topical steroids — which may be associated with significant safety risks when used long-term. This has left patients and their caregivers in desperate need of medicines that can better address the chronic, long-term nature of the disease,” Naimish Patel, MD, senior vice president and head of global development in immunology and inflammation at Sanofi, said in the release. “These young people, and their families, often struggle to cope with the significant impact itch can have not only on the body, but on many other facets of daily life. This approval means that Dupixent, with its well-established safety and efficacy profile, is now available to some of the youngest people living with this disease.”

The drug’s safety profile in this younger age group was similar to the safety profile in the 6 years and older group, with hand, foot and mouth disease and skin papilloma being the most common treatment emergent adverse events recorded.

“We are not seeing any new red flags, and that means we have a systemic that even though it is injectable, it doesn’t need any lab testing. Safety is what speaks volumes to those of us who treat pediatric patients and certainly to the families of those patients,” Paller said.

Serious Infection Risk with Biologics for Atopic Dermatitis

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Off-label use of biologic agents to treat refractory atopic dermatitis posed a significant risk of serious infection as compared with systemic nonbiologic agents, data on almost 400,000 patients showed.

A propensity-matched analysis showed that treatment with a biologic agent doubled the risk of hospitalization for a serious bacterial or opportunistic infection as compared with high-potency topical steroids or nonbiologic systemic therapy. Infection risk also varied substantially among nonbiologic systemic agents, with cyclosporine posing the lowest risk and azathioprine and mycophenolate the greatest risk, as reported here at the European Academy of Dermatology and Venereology congress.

“This is the largest comparative safety evaluation of its kind to date in adult patients with atopic dermatitis,” said Mia Schneeweiss, a student at Harvard Medical School and Brigham and Women’s Hospital in Boston. “Biologics were associated with a greater risk of serious infection requiring hospitalization than either nonbiologic systemics or topical steroids.”

The analysis did not include patients treated with newer biologic agents specifically approved for atopic dermatitis, such as dupilumab (Dupixent). Investigators intend to update the analysis with data on outcomes with the newer agents, as well as long-term outcomes with all the treatments, she added.

The study had its genesis in the increasing use of systemic nonbiologic immunomodulatory drugs and systemic biologic agents to treat atopic dermatitis that is inadequately controlled by topical steroids. Mixed results have emerged from studies use of biologic agents to treatment recalcitrant atopy; however, experience with systemic biologic and nonbiologic agents in other conditions (such as psoriasis and rheumatoid arthritis) has shown an increased risk of bacterial infections, Schneeweiss noted.

“Few population-based studies have evaluated the safety of off-label use of these systemic agents for treating severe atopic dermatitis,” she said. “Additionally, comparative safety data among nonbiologic and biologic immunomodulatory agents in the treatment of atopic dermatitis is limited.”

In an effort increase the evidence base, investigators undertook an analysis of a commercial insurance claims database encompassing 2003-2016 and 180 million lives. They used diagnostic codes to identify all adults with a diagnosis of atopic dermatitis and initiating treatment. Patients with other indications for any of the medications of interest (psoriasis, arthritis, organ transplantation, etc.) were excluded.

The primary outcome was first occurrence of hospitalization for a serious bacterial or opportunistic infection. Patient characteristics were assessed 6 months before the study and followed for an additional 6 months.

The study consisted of two cohort analyses. The first involved patients who initiated treatment with a low-potency topical corticosteroid and subsequently had treatment escalation to one of three therapeutic categories: high-potency topical corticosteroids, biologics and disease-modifying drugs (including anti-TNF agents, rituximab [Rituxan], and tofacitinib [Xeljanz], and nonbiologic systemic therapy (methotrexate, cyclosporine, azathioprine, prednisone, and mycophenolate).

The second cohort comprised patients who started treatment with any type of topical corticosteroid and subsequently had treatment escalation to a biologic or systemic nonbiologic agent.

The first cohort included 396,734 patients who initiated treatment with a high-potency topical corticosteroid and 403 patients who started treatment with a biologic agent. The second cohort included 153,890 patients who initiated treatment with a systemic nonbiologic agent and 2,116 who who started a biologic drug.

In the first cohort, patients who escalated to a high-potency topical steroid had a total of 1,039 qualifying hospitalizations for serious infection, resulting in a rate of 2.62 per 1,000. That compared with 16 events in the 403 patients who initiated treatment with a biologic agent, resulting in a rate of 39.70 per 1,000. An unadjusted analysis produced a relative risk of 15.16 for patients treated with biologics.

The second cohort analysis showed 1,239 hospitalizations for infection in the patients who were new users of systemic nonbiologic agents (8.05/1,000) versus 47 hospitalizations among new users of biologic therapies (22.21/1,000). Comparison of the two groups yielded a relative risk of 2.76 for the patients who received biologic therapy.

A multivariate analysis with propensity matching yielded similar relative risks for the two cohorts: 2.74 for the comparison of biologics versus high-potency topical corticosteroids and 2.16 for the comparison of biologics versus systemic nonbiologic agents.

Investigators also compared the relative risk of infection-related hospitalization for the five systemic nonbiologic agents. Cyclosporine emerged with the lowest overall relative risk, ranging from 0.17 to 0.55 in comparisons with other four systemic nonbiologic, followed by prednisone and methotrexate. Mycophenolate was associated with the highest relative risk (1.64 to 5.88), and azathioprine had a two- to fourfold higher risk versus all other agents except mycophenolate

Effect of Oral Administration of a Mixture of Probiotic Strains on SCORAD Index and Use of Topical Steroids in Young Patients With Moderate Atopic Dermatitis

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Key Points

Question  Can treatment with an oral probiotic reduce the SCORAD index and the use of topical steroids in children with moderate atopic dermatitis?

Findings  This randomized clinical trial of 50 children treated with a mixture of probiotics or placebo for 12 weeks found that SCORAD and topical steroid use decreased significantly in the probiotic group compared with the placebo group.

Meaning  This probiotic is an effective and safe coadjuvant treatment to reduce the SCORAD index and topical steroid use in children with moderate atopic dermatitis.

Abstract

Importance  Oral intake of new probiotic formulations may improve the course of atopic dermatitis (AD) in a young population.

Objective  To determine whether a mixture of oral probiotics is safe and effective in the treatment of AD symptoms and to evaluate its influence on the use of topical steroids in a young population.

Design, Setting, and Participants  A 12-week randomized, double-blind, placebo-controlled intervention trial, from March to June 2016, at the outpatient hospital Centro Dermatológico Estético de Alicante, Alicante, Spain. Observers were blinded to patient groupings. Participants were children aged 4 to 17 years with moderate atopic dermatitis. The groups were stratified and block randomized according to sex, age, and age of onset. Patients were ineligible if they had used systemic immunosuppressive drugs in the previous 3 months or antibiotics in the previous 2 weeks or had a concomitant diagnosis of intestinal bowel disease or signs of bacterial infection.

Interventions  Twelve weeks with a daily capsule containing freeze-dried powder with 109 total colony-forming units of the probiotic strains Bifidobacterium lactis CECT 8145, B longum CECT 7347, and Lactobacillus casei CECT 9104 and maltodextrin as a carrier, or placebo (maltodextrin-only capsules).

Main Outcomes and Measures  SCORAD index score and days of topical steroid use were analyzed.

Results  Fifty children (26 [50%] female; mean [SD] age, 9.2 [3.7] years) participated. After 12 weeks of follow-up, the mean reduction in the SCORAD index in the probiotic group was 19.2 points greater than in the control group (mean difference, −19.2; 95% CI, −15.0 to −23.4). In relative terms, we observed a change of −83% (95% CI, −95% to −70%) in the probiotic group and −24% (95% CI, −36% to −11%) in the placebo group (P < .001). We found a significant reduction in the use of topical steroids to treat flares in the probiotic arm (161 of 2084 patient-days [7.7%]) compared with the control arm (220 of 2032 patient-days [10.8%]; odds ratio, 0.63; 95% CI, 0.51 to 0.78).

Conclusions and Relevance  The mixture of probiotics was effective in reducing SCORAD index and reducing the use of topical steroids in patients with moderate AD.

Source:jamanetwork.com

Probiotics May Improve Pediatric AD Symptoms

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Probiotics may also reduce need for topical corticosteroids

A daily capsule of a cocktail of probiotics may reduce both the severity symptoms in moderate atopic dermatitis and the need for topical corticosteroids to treat symptom flare ups in children, research published in JAMA Dermatology suggests.

In recent years, research has demonstrated close links between gut microflora and many factors involved in the pathogenesis of atopic dermatitis, such as immunity. Patients with atopic dermatitis have been shown to have different faecal microbiota compared to healthy control subjects, and the composition and diversity of the gut microbiota of young children who later developed atopic dermatitis have been shown to be different from those of children who did not.

Up to 20% of children are affected by atopic dermatitis and a group of researchers based in Spain decided to test whether there was a potential role for probiotics in their treatment.

Lead author Vicente Navarro-López, MD, PhD, of the Universidad Católica San Antonio de Murcia (UCAM) in Spain, said: “Several studies have already explored the efficacy of certain probiotics in the prevention and treatment of atopic dermatitis. Overall, the current evidence suggests that probiotics could be an option to improve moderate and severe atopic dermatitis recovery rates in children and adults; however, to date, there is no strong experimental evidence supporting their effectiveness and safety in clinical practice.

Importantly, evidence and clinical trials demonstrating strain-specific effects are lacking.”

The study

The group conducted a double-blind, placebo-controlled trial, between March and June 2016, at a hospital in Alicante, Spain. The study involved 50 children, ages 4 to 17 years with moderate atopic dermatitis, who were randomized according to sex, age, and age of onset of atopic dermatitis to a daily capsule containing freeze-dried powder with 109 total colony-forming units of the probiotic strains Bifidobacterium lactis CECT 8145, B longum CECT 7347, and Lactobacillus casei CECT 9104 and maltodextrin as a carrier, or maltodextrin-only capsules (placebo) for 12 weeks. None of the children involved had received systemic immunosuppressive drugs in the previous three months or antibiotics in the previous two weeks, and none had a diagnosed intestinal bowel disease or signs of bacterial infection.

After 12 weeks children who had taken probiotics saw a 19.2 points greater reduction in the SCORAD (Scoring Atopic Dermatitis) index than those who took the placebo capsule (mean difference, −19.2; 95%CI, −15.0 to −23.4). In relative terms, the SCORAD index fell by 83% in the probiotic group (95%CI, −95% to −70%) compared to 24% (95%CI, −36%to −11%) in the placebo group (P<0.001).

Two of the sub-components of the SCORAD index (eczema spread and intensity) showed clear improvement in the children who took probiotics compared with those who took placebo, but there was no statistically significant difference in the third sub-component – subjective symptoms. In the probiotic group subjective symptoms fell by 77%, but they also fell substantially in the placebo group – by 53%.

Navarro-López suggested that this might be because patients who took placebo might have been able to reduce symptoms such as pruritus by using more corticosteroids.

The usual treatment for mild-to-moderate atopic dermatitis is a course of topical corticosteroids, and long term topical steroids for moderate to severe disease.

Children who took probiotics in the study used topical steroids to treat atopic dermatitis flare ups on significantly fewer days (161 of 2084 patient-days [7.7%]) than those who took the placebo capsule (220 of 2032 patient-days [10.8%]; odds ratio, 0.63; 95%CI, 0.51 to 0.78).

Navarro-López said: “Our results suggest that administration of this mixture of probiotics, as adjuvant treatment, may be effective in reducing the SCORAD index and, subsequently, decreasing the use of steroids during atopic dermatitis flares.”

He added that the clinical response documented in the probiotic group was greater than that obtained with other probiotics tested previously and suggested that a greater effect may have been seen due to the longer length of treatment and the patients involved in this particular trial.

“Treatment longer than eight weeks might condition the positive effect of probiotic use, patients older than 1 year have a greater response to probiotics, patients with moderate to severe atopic dermatitis have a better response, and a mixture of probiotics has better beneficial effects than a single probiotic, especially when lactobacilli and bifidobacteria are included in the mixture,” he said.

“The final blend used in the study was selected on the basis of published results and internal unpublished data,” he added.

The physiology of gut microbiota in atopic derm

So how might gut microbiota be implicated in atopic dermatitis and probiotics exert their effects?

It has been suggested that there is an association between a disruption in intestinal barrier function and the origin of atopic dermatitis, mediated by immunological activation leading to a type 2 dominant inflammation, which would suggest that gut microbiota could play an important immunomodulatory role in the development of normal immune tolerance. A predominance of T helper two cells rather than T helper 1, causes an imbalance that might aggravate the pathogenesis of atopic dermatitis, increasing IgE and activating interleukins.

Low levels of Faecalibacterium prausnitzii and an associated reduction in short chain fatty acid production have been implicated in Crohn’s disease, and a recent analysis of the gut microbiota of patients with atopic dermatitis has shown an intra-species compositional change in Faecalibacterium prausnitzii that reduces the number of high butyrate and propionate producers.

Butyrate and propionate are microbial-produced short-chain fatty acids with an anti-inflammatory role, and butyrate has been shown to be a key player in maintaining gut barrier integrity. Therefore, reduced levels in the microbiota of both butyrate and propionate producers may result in a pro-inflammatory state in the gut and a loss of barrier integrity.

This raises a potential role for probiotics as microbiota recovery players in atopic dermatitis, Navarro-López said.