Systemic treatments for atopic dermatitis (eczema): Systematic review and network meta-analysis of randomized trials.

BACKGROUND: Atopic dermatitis (AD) is an inflammatory skin condition with multiple systemic treatments and uncertainty regarding their comparative impact on AD outcomes. OBJECTIVE: We sought to systematically synthesize the benefits and harms of AD systemic treatments. METHODS: For the 2023 American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma, and Immunology Joint Task Force on Practice Parameters AD guidelines, we searched MEDLINE, EMBASE, CENTRAL, Web of Science, and GREAT databases from inception to November 29, 2022, for randomized trials addressing systemic treatments and phototherapy for AD. Paired reviewers independently screened records, extracted data, and assessed risk of bias. Random-effects network meta-analyses addressed AD severity, itch, sleep, AD-related quality of life, flares, and harms. The Grading of Recommendations Assessment, Development and Evaluation approach informed certainty of evidence ratings. This review is registered in the Open Science Framework (https://osf.io/e5sna). RESULTS: The 149 included trials (28,686 patients with moderate-to-severe AD) evaluated 75 interventions. With high-certainty evidence, high-dose upadacitinib was among the most effective for 5 of 6 patient-important outcomes; high-dose abrocitinib and low-dose upadacitinib were among the most effective for 2 outcomes. These Janus kinase inhibitors were among the most harmful in increasing adverse events. With high-certainty evidence, dupilumab, lebrikizumab, and tralokinumab were of intermediate effectiveness and among the safest, modestly increasing conjunctivitis. Low-dose baricitinib was among the least effective. Efficacy and safety of azathioprine, oral corticosteroids, cyclosporine, methotrexate, mycophenolate, phototherapy, and many novel agents are less certain. CONCLUSIONS: Among individuals with moderate-to-severe AD, high-certainty evidence demonstrates that high-dose upadacitinib is among the most effective in addressing multiple patient-important outcomes, but also is among the most harmful. High-dose abrocitinib and low-dose upadacitinib are effective, but also among the most harmful. Dupilumab, lebrikizumab, and tralokinumab are of intermediate effectiveness and have favorable safety.

Systemic Reactions in Pediatric Patients Receiving Standardized Allergen Subcutaneous Immunotherapy with and without Seasonal Dose Adjustment.

BACKGROUND: The 2003 Joint Task Force on Practice Parameters recommended standardizing allergen subcutaneous immunotherapy (SCIT). Data from longitudinal surveillance survey in North America reported a systemic reaction (SR) rate of 0.1% to 0.2% of injection visits. The rate of SR to standardized SCIT in pediatric patients has not been well evaluated. OBJECTIVE: The objective of this study was to evaluate the rate of SRs to standardized SCIT in pediatric patients aged 5 to 18 years in a single tertiary care center in the United States. METHODS: A retrospective chart review was conducted in 2 groups: group 1 started SCIT within a period extending from January 2009 to June 2012, whereas group 2 started SCIT within a period extending from January 2013 to June 2016. The protocol was modified in group 2 such that updosing and maintenance doses were adjusted in the spring for tree and grass pollen and in the fall for weed pollen. RESULTS: There were a total of 128 patients in group 1 and 118 patients in group 2. The rate of SR was 0.429% in group 1 and 0.364% in group 2, which was not significant. There was no difference in the severity of SR in the 2 groups with no-fatal or near-fatal SR noted. Asthma was a significant risk factor in the younger age subgroup aged 5 to 11 years. CONCLUSIONS: Standardized SCIT appears to be associated with an SR rate of 0.429% to 0.364% of visits in pediatric patients. Protocol modification did not lead to a significant drop in SR. Larger multicenter studies are required to further evaluate the rate of SRs from standardized SCIT.

Management of difficult-to-treat atopic dermatitis.

Atopic dermatitis is a complex disorder caused by the interplay between multiple genetic and environmental factors. Particularly in patients with severe disease, the effect is not just an itchy rash but also the secondary effects on the psychological well-being of the patient and their carers, particularly disturbed sleep. The aim of this review is to provide health care professionals with a holistic approach to the management of difficult-to-treat atopic dermatitis, defined as atopic dermatitis seemingly unresponsive to simple moisturizers and mild potency (classes VI and VII) topical corticosteroids. The critical importance of education and advice is emphasized, as is the seminal role of secondary bacterial infection and polyclonal T-cell activation in causing acute flares in patients with severe, generalized disease. In atypical cases or those that do not respond to treatment, alternative diagnoses should be considered.

Integrating medical and psychological health care for children with atopic dermatitis.

OBJECTIVE: To present descriptive data from a hospital-based interdisciplinary program that provides integrated medical and psychological health-care for children with atopic dermatitis (AD). METHODS: Clinical records were reviewed for 69 children seen in our program to examine parent-reported AD-related presenting concerns, as well as common problems and interventions addressed during family visits with the program psychologist. RESULTS: The most common presenting concerns included child itching and scratching and associated sleep problems. Parent initial request for a meeting with the program psychologist was not related to child disease severity, but was associated with child sleep problems and parent emotional and practical challenges in managing the child's condition. CONCLUSIONS: Results support the need for, acceptance of, and feasibility of providing integrated care for children with AD and their families. Changes to our clinical model based on study findings are discussed.

Assessment of adrenal suppression in children with asthma treated with inhaled corticosteroids: use of dehydroepiandrosterone sulfate as a screening test.

BACKGROUND: Inhaled corticosteroids (ICs) are considered first-line therapy for persistent asthma. At medium to high doses, ICs can suppress the hypothalamic-pituitary-adrenal (HPA) axis. Various provocative stimuli have been used to evaluate HPA axis function, but they are labor intensive and time-consuming. Dehydroepiandrosterone sulfate (DHEA-S) is a corticotropin-dependent adrenal androgen precursor that is suppressible in patients treated with ICs. OBJECTIVES: To evaluate DHEA-S as a possible marker for HPA axis dysfunction in children treated with ICs. METHODS: Children with moderate-to-severe persistent asthma and a history of medium- to high-dose IC exposure for at least 6 months were evaluated using low-dose and standard high-dose cosyntropin stimulation testing to assess adrenal function, and DHEA-S levels were compared with the results. RESULTS: Thirteen (59%) of 22 patients exhibited an abnormal cortisol response to cosyntropin. Age- and sex-specific mean DHEA-S z scores were significantly lower in cosyntropin abnormal responders (-1.2822) compared with normal responders (0.2964) (P = .008). The receiver operating characteristic curve for DHEA-S z scores had an area of 0.786 (95% confidence interval, 0.584-0.989), reaching 100% sensitivity with a DHEA-S z score of -1.5966 or less and 100% specificity with a DHEA-S z score greater than 0.0225. CONCLUSIONS: Most children develop biochemical evidence of adrenal suppression after treatment with medium to high doses of ICs. The presence of low DHEA-S levels can be used as a screening test to identify the child who needs more formal testing of the HPA axis.