Leukotriene receptor antagonists as add-on therapy to antihistamines for urticaria: Systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: The benefits and harms of adding antileukotrienes to H1 antihistamines (AHs) for the management of urticaria (hives, itch, and/or angioedema) remain unclear. OBJECTIVE: We sought to systematically synthesize the treatment outcomes of antileukotrienes in combination with AHs versus AHs alone for acute and chronic urticaria. METHODS: As part of updating American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma, and Immunology Joint Task Force on Practice Parameters urticaria guidelines, we searched Medline, Embase, Central, LILACS, WPRIM, IBECS, ICTRP, CBM, CNKI, VIP, Wanfang, US Food and Drug Administration, and European Medicines Agency databases from inception to December 18, 2023, for randomized controlled trials (RCTs) evaluating antileukotrienes and AHs versus AHs alone in patients with urticaria. Paired reviewers independently screened citations, extracted data, and assessed risk of bias. Random effects models pooled effect estimates for urticaria activity, itch, wheal, sleep, quality of life, and harms. The GRADE approach informed certainty of evidence ratings. The study was registered at the Open Science Framework (osf.io/h2bfx/). RESULTS: Thirty-four RCTs enrolled 3324 children and adults. Compared to AHs alone, the combination of a leukotriene receptor antagonist with AHs probably modestly reduces urticaria activity (mean difference, -5.04; 95% confidence interval, -6.36 to -3.71; 7-day urticaria activity score) with moderate certainty. We made similar findings for itch and wheal severity as well as quality of life. Adverse events were probably not different between groups (moderate certainty); however, no RCT reported on neuropsychiatric adverse events. CONCLUSION: Among patients with urticaria, adding leukotriene receptor antagonists to AHs probably modestly improves urticaria activity with little to no increase in overall adverse events. The added risk of neuropsychiatric adverse events in this population with leukotriene receptor antagonists is small and uncertain.

Topical corticosteroids for hives and itch (urticaria): Systematic review and Bayesian meta-analysis of randomized trials.

BACKGROUND: Topical corticosteroids are widely used as a treatment for itch and wheals (urticaria), but their benefits and harms are unclear. OBJECTIVE: To systematically synthesize the benefits and harms of topical corticosteroids for the treatment of urticaria. METHODS: We searched MEDLINE, EMBASE, and CENTRAL from database inception to March 23, 2024, for randomized trials comparing topical corticosteroids with placebo for patients with urticaria (either chronic spontaneous or inducible urticaria or acute urticaria elicited from skin/intradermal allergy testing). Paired reviewers independently screened records, extracted data, and assessed risk of bias. Random-effects meta-analyses addressed urticaria severity, itch severity (numeric rating scale; range 0-10; higher is worse), and adverse events. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach informed certainty of evidence ratings. PROSPERO registration: CRD42023455182. RESULTS: A total of 19 randomized controlled trials enrolled 379 participants with a median of mean age of 30.1 (range 21.1-44.0) years. Compared with placebo, topical corticosteroids may reduce wheal size (ratio of means 0.47, 95% CI 0.38-0.59; low certainty) and itch severity (mean difference -1.30, 95% CI -5.07 to 2.46; very low certainty). Topical corticosteroids result in little to no difference in overall adverse events (94 fewer patients per 1000, 95% credible intervals 172 fewer to 12 more; high certainty). CONCLUSION: Compared with placebo, topical corticosteroids may result in a reduction of wheal size and little to no difference in overall adverse events. Topical corticosteroids may reduce itch severity, but the evidence is very uncertain. Future large, randomized trials addressing the use of topical corticosteroids would further support optimal urticaria management.

Correlation between PainDETECT Questionnaire and Quantitative Sensory Testing for the Detection of Neuropathic Pain in Hidradenitis Suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that is often severely painful due to nociceptive mechanisms (i.e., stimulation of cutaneous nociceptors). However, patient-reported pain character suggests that neuropathy may also drive HS pain in a subset of patients. Quantitative sensory testing (QST) can help identify neuropathic pain by testing for heightened and paradoxical pain responses in patients, but it is less feasible for routine clinical use compared with brief questionnaires. We therefore tested the suitability of a standardized neuropathic questionnaire (PainDETECT; PD-Q) for use as a surrogate clinical measure by directly comparing it with QST-identified neuropathic pain in HS. METHODS: This observational, cross-sectional study included 22 adults with painful HS lesions who completed the PD-Q and underwent QST. A receiver operating characteristic curve was generated and Cohen's Kappa, sensitivity, and specificity were examined at three scoring thresholds. RESULTS: Of the 22 participants, 14 (64%) exhibited dynamic mechanical allodynia and/or paradoxical thermal sensations in QST, which are characteristically found in neuropathic pain. According to the PD-Q, 8 participants (36%) were unlikely, 8 (36%) were possible, and 6 (27%) were likely to have neuropathic pain. A PD-Q Score indicating possible or likely neuropathic pain (i.e., ≥13) demonstrated 82% agreement with QST-determined neuropathic pain (Cohen's Kappa = 0.61 [p = 0.004]; sensitivity = 86%; specificity = 75%). CONCLUSION: The PD-Q demonstrates moderate agreement with QST in screening for neuropathic pain in HS and may be a helpful clinical tool.

Comparing Clinical Outcomes of Steroid-Sparing Therapy With Rituximab Versus Rituximab Alone in Pemphigus.

BACKGROUND: Previous clinical trials have demonstrated that rituximab therapy combined with conventional steroid-sparing therapy (SST) has increased rates of disease control for mucous membrane pemphigoid compared with rituximab alone. However, limited data is available regarding the role of SST with rituximab therapy in pemphigus. OBJECTIVE: This study aimed to examine clinical outcomes in pemphigus patients treated with rituximab with SST versus without the addition of SST. METHODS: A retrospective chart review was performed for adult pemphigus patients in the Southeastern US at Emory between January 1, 2011, and December 31, 2021. Primary outcomes, including time to remission, time to prednisone dose of 10 mg or less, time to cessation of prednisone therapy, and time to relapse after a rituximab cycle, were compared between patients on SST and patients without SST.  Results: Following rituximab therapy, there was no difference in time to remission, time to prednisone dose of 10 mg or less, time to cessation of prednisone therapy, or time to relapse for patients with or without SST. LIMITATIONS: Our study is limited by its retrospective decline, setting at a single academic center, and inclusion of a high proportion of patients with moderate disease. CONCLUSIONS: The use of SST with rituximab dosing did not improve clinical outcomes related to time to remission, reduction in prednisone dosing, or relapse. These data provide further evidence for the use of rituximab in the majority of pemphigus patients without the need for SST. J Drugs Dermatol. 2024;23(3):e97-e99    doi:10.36849/JDD.7949e.

Childhood atopic dermatitis is associated with cognitive dysfunction: A National Health Interview Survey study from 2008 to 2018.

BACKGROUND: Atopic dermatitis (AD) is a common inflammatory skin disease in children and adults. Little is known regarding the association of childhood AD with cognitive dysfunction. OBJECTIVE: To evaluate the association of AD and cognitive dysfunction, including memory impairment, developmental delays and attention deficit (hyperactivity) disorder in US children (age <18 years). METHODS: Data was analyzed from the National Health Interview Survey 2008 to 2018, which used a multistage, clustered, cross-sectional design. RESULTS: The prevalences of cognitive dysfunction, such as memory impairment (0.87% vs 0.42%), developmental delays (6.96% vs 3.87%), and attention deficit (hyperactivity) disorder (10.78% vs 8.10%), were higher in children with vs without AD. In multivariable logistic regression models adjusting for age, sex, race, region, socioeconomic factors, allergic conditions, and mental health, childhood AD was associated with higher odds of memory impairment (adjusted odds ratio [95% confidence interval]: 1.84 [1.34-2.51]), developmental delays (1.54 [1.40-1.70]), and attention deficit (hyperactivity) disorder (1.31 [1.20-1.42]) compared with children without AD. Childhood atopic disease (defined as comorbid AD, asthma, allergic rhinitis, and food allergies) further increased the prevalence of developmental delays to 13.44% (2.10 [1.20-3.70]) in boys but not in girls. CONCLUSION: In a nationally representative sample of the US population, a statistically significant and positive association between childhood AD and atopic disease with cognitive dysfunction was identified (P < .001). Furthermore, a dimorphic relationship with developmental delays was identified between sexes.

TH2 sensitization in the skin-gut-brain axis: How early-life Th2-mediated inflammation may negatively perpetuate developmental and psychologic abnormalities.

We recently reported children with comorbid atopic dermatitis (AD), asthma, allergic rhinitis, and food allergies displaying a 2.7-fold increase in developmental delays.2 To this end, we hypothesize unregulated increases in T helper-2 (Th2)-driven inflammation, such as those seen in atopic diseases, can exert deleterious effects on the developing brain. Recognizing that available information is incomplete and that many potential associations are not firmly established, we speculate these effects underlie the association between Th2 sensitization and cognitive dysfunction in children. In this review, we explore the role of Th2 sensitization in the skin-gut-brain axis and explain how it can lead to reduced connectivity and transmission in the developing brain. With a focus on AD, we explore the association between Th2 sensitization and developmental abnormalities such as developmental delays, memory impairment, autism spectrum disorder (ASD), and epilepsy/seizures. As such, we review the available literature to examine the impact of increased IL-4 exposure in early life on the brain. We explore the possible association between Th2 sensitization and psychologic dysfunction such as attention-deficit/hyperactivity disorder (ADHD), depression, anxiety, and suicidal ideation. We also examine the impact that increased exposure to glucocorticoids and neurotrophins in early life exerts on the developing brain. Last, we discuss future directions for the advancement of our knowledge as a scientific community including possible interventions to reduce developmental and psychologic aberrations in children.

The Effects of Surgery Type and Chemotherapy on Early-Stage Breast Cancer Patients' Quality of Life Over 2-Year Follow-up.

BACKGROUND: We examined the effects of surgery type and adjuvant chemotherapy on change in early-stage breast cancer patients' quality of life (QOL) over time. METHODS: A cohort of 549 patients (33.5% ductal carcinoma in situ, 66.5% stages I/IIA) were interviewed a mean 6.1 weeks (Time1), and 6.2 (Time2), 12.3 (Time3), and 24.4 (Time4) months following definitive breast-conserving surgery (BCS) or mastectomy. QOL was measured using the total Functional Assessment of Cancer Therapy-Breast (FACT-B). Adjusting for demographic, psychosocial, and clinical variables, multiple linear regression models estimated the associations between QOL and each of surgery type, chemotherapy, and their 2-way interaction at each interview. Adjusted generalized estimating equation (GEE) models tested Time1-Time4 change in QOL. RESULTS: At Time2, chemotherapy (P < .001) and BCS (P < .001) were independently associated with worse QOL in adjusted linear regression, and the adverse effect of chemotherapy was prominent among patients who received BCS compared with those who received mastectomy (P interaction = .031). In the GEE model, QOL significantly improved over time among patients who received BCS (P trend = .047), mastectomy (P trend = .024), and chemotherapy (P trend < .001), but not among patients who did not receive chemotherapy (P trend = .720). All patients completed adjuvant chemotherapy and radiation by Time3. Regardless of surgery type, patients receiving chemotherapy reported lower QOL following surgery, and QOL improved after completion of adjuvant treatment. CONCLUSIONS: Chemotherapy had a short-term negative impact on QOL after definitive surgical treatment regardless of surgery type. QOL rebounded after completion of adjuvant treatment.