Five Interventions to Demote
Oral H1 Antihistamines
Oral antihistamines are commonly prescribed in addition to topical treatments to alleviate itch in eczema. The sedating effects of first-generation antihistamines are sometimes used to manage the sleep disturbances in eczema due to itching, particularly in children. A Cochrane review investigating oral H1 antihistamines as an 'add-on' treatment in adults and children with eczema collated evidence from 25 RCTs and 3285 participants. Though antihistamines were assessed as being safe, no consistent evidence was found to indicate that H1 antihistamines, including cetirizine and loratadine, were more effective when compared to placebo. Though fexofenadine showed a small improvement in patient-rated pruritus (MD 0.25 [95% CI 0.43–0.07] point improvement on a scale of 0–8), no significant difference in the quantity of treatment used to prevent flares of eczema was found. There is little evidence, therefore, to continue the routine use of oral antihistamines in eczema management, perhaps with the exception of those with concomitant urticarial lesions and allergic rhinitis/hay fever with associated periorbital eczema.
Antistaphylococcal Treatments: Unless Systemically Unwell
The management of overt secondary infection and colonization of the skin by Staphylococcus aureus in eczema is a contentious topic, with high variation in practice between clinicians and in primary versus secondary care settings. S. aureus is rarely found on healthy skin (in <5%) and is identified in approximately 70% of eczematous skin lesions. Various antistaphylococcal treatments are often used in the management of eczema flares, including systemic and topical antibiotics (sometimes in combination with TCS). A Cochrane review of antistaphylococcal treatments in children and adults with eczema included 41 studies and 1753 participants. In the treatment of both clinically infected and uninfected eczema, there was insufficient evidence to support the use of antistaphylococcal treatments. Apart from a high quality recent pivotal trial, the evidence was generally poor and studies were quite heterogeneous, limiting the ability to pool results. Given the serious concerns that overuse of antibiotics will contribute to antimicrobial resistance and the absence of evidence of benefit in eczema, the use of antistaphylococcal treatments should be demoted in routine clinical practice, unless a patient is systemically unwell, a position that is supported by recent guidance from the UK National Institute for Health and Care Excellence.
Probiotics are orally ingested live microorganisms that are purported to benefit people with active eczema. An updated Cochrane review of RCTs on this topic published in 2018 included 39 RCTs of 2599 participants. The review found little evidence to support the use of probiotics in eczema, with little to no difference in quality-of-life outcomes (SMD 0.03 worse [95% CI 0.36 better to 0.42 worse], GRADE low certainty evidence) and in investigator-rated disease severity scores (MD total SCORAD score in the intervention groups was 3.91 points lower [95% CI 5.86–1.96 points lower], GRADE low certainty evidence; MCID 8.7); significant heterogeneity between studies was observed. A trial sequential analysis was conducted (Figure 3), indicating that future RCTs of probiotics are unlikely to change the conclusion that a two-point difference in eczema symptoms (measured by SCORAD) between probiotic and no probiotic will be found.
Trial sequential analysis: for a minimum difference of −2 points difference in eczema symptoms (SCORAD part C; range 0–20) between probiotics and no probiotics (90% power). Blue z-curve of meta-analysis shows that optimal heterogeneity-adjusted information size has been reached. Reproduced with permission from .
Some 'Nonpharmacological' Interventions Including Silk Clothing, Water Softeners and Bath Emollients
Various nonpharmacological interventions are also often considered for eczema management, some of which have been investigated in trial settings. The role of silk clothing was tested in children with moderate to severe eczema in an observer-blind RCT (the CLOTHES trial). Silk garments were worn for 6 months in the intervention group and both groups received usual standard care. The primary outcome measure was the Eczema Area and Severity Index (EASI) score (MCID 6.6). Results failed to show any additional improvement with wearing silk garments (EASI score averaged over all follow-up visits adjusted for baseline EASI score, age, and centre: adjusted ratio of geometric means 0.95 [95%CI 0.85 to 1.07; this 95%CI is equivalent to a difference of −1.5 to 0.5 in the original EASI units, which is not clinically important).
The SWET trial investigated whether the installation of an ion-exchange water softener in the home of children who live in hard water areas (≥200 mg/l calcium carbonate) can improve eczema. This observer-blind RCT of 336 children with moderate-to-severe eczema identified no additional benefit in the intervention group (Six Area, Sign Sign Atopic Dermatitis severity score [range 0–108] at 12 weeks, 0.66 [95% CI −1.37–2.69]); both groups continued usual standard care without reported differences in topical anti-inflammatory use.
The BATHE trial was a multicentre pragmatic parallel group RCT conducted to determine the effect of emollient bath additives in the treatment of childhood eczema. Four hundred eighty-three children were randomized to either standard care (which included direct application of emollients and TCSs) or standard care plus the use of bath additives regularly for 12 months. The primary outcome measure was the Patient Orientated Eczema Measure (POEM) score, which was measured weekly for 16 weeks. No clinically important or statistically significant differences were observed between groups (after controlling for baseline severity and confounders (ethnicity, topical corticosteroid use, soap substitute use) and allowing for clustering of participants within centres and responses within participants over time, POEM scores in the no bath additives group were 0.41 [95% CI −0.27–1.10] points higher [worse] than in the bath additives group, below the published minimal clinically important difference for POEM of three points). Together, these three large independent RCTs suggest no additional benefits with the use of silk clothing, water softeners and bath emollient additives.
Emollients for Eczema Prevention
The Barrier Enhancement for Eczema Prevention (BEEP) trial sought to investigate whether daily emollient use in term infants at high risk of developing eczema (having at least one first degree relative with clinically diagnosed eczema, asthma or hayfever) could reduce the risk of developing eczema by the age of 2 years. 1394 newborns were randomized and adherence in both groups was high. Daily emollient use did not prevent eczema in these high-risk infants, a result that was replicated in a similar Scandinavian study of 2397 high-risk children. These studies also suggested that emollients were associated with a small increased risk of skin infections and a nonsignificant increase in food allergy. A subsequent Cochrane prospectively planned individual patient meta-analysis that included 17 studies that randomized 5823 participants to emollients for eczema prevention found that emollient use in infancy did not change the risk of eczema by 1–2 years of age (RR 1.03, 95% CI 0.81–1.31; moderate-certainty evidence; 3075 participants, seven trials) nor time to onset of eczema (hazard ratio 0.86, 95% CI 0.65–1.14; moderate-certainty evidence; 3349 participants, nine trials). Another study found that increased use of moisturizers in infancy may promote food allergies, with each additional weekly application associated with an adjusted odds ratio of 1.20 (95% CI 1.13–1.27) for developing food allergy.
Curr Opin Allergy Clin Immunol. 2021;21(4):386-393. © 2021 Lippincott Williams & Wilkins