an2728 and Pain

The prevalence of atopic dermatitis (AD) in geriatric populations of industrialized countries is currently estimated at 3-4% and continues to increase. AD is associated with significant morbidity, increased susceptibility to infection, and symptoms of pruritus and pain. Treatments may negatively affect elderly patients; thus, plans should be optimized for this population.. This review summarizes treatment options for AD in the elderly. A systematic review of the literature was conducted using the key terms atopic dermatitis, elderly, geriatric, systemic therapy, therapy, and topical therapy in PubMed. Searches yielded articles on skincare management and topical and systemic pharmacotherapies.. Proper use of moisturizer is crucial in all patients with AD. Topical corticosteroids are commonly prescribed; however, they carry an increased risk of adverse events such as skin atrophy. Systemic corticosteroids should be avoided in elderly patients due to questionable efficacy and increased adverse events. Topical calcineurin inhibitors and crisaborole are similarly efficacious with an excellent safety profile. Cyclosporine, azathioprine, methotrexate, and mycophenolate mofetil are systemic agents available for the treatment of refractory AD; however, insufficient data exist to indicate the superiority of any one agent. Dupilumab is a safe and efficacious injectable therapy in elderly patients.

Topics: Aged; Antibodies, Monoclonal, Humanized; Boron Compounds; Bridged Bicyclo Compounds, Heterocyclic; Calcineurin Inhibitors; Cyclosporine; Dermatitis, Atopic; Dermatologic Agents; Humans; Pain; Pruritus; Treatment Outcome

Herein we review recent developments in our understanding and treatment of atopic dermatitis. Key insights from the recent literature are summarized, from findings on the pathogenesis of this multifactorial disease to a new and more nuanced understanding of its natural history. Therapeutic advances and new data on comorbidities are also discussed.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Baths; Boron Compounds; Bridged Bicyclo Compounds, Heterocyclic; Comorbidity; Dermatitis, Atopic; Dermatologic Agents; Environmental Exposure; Humans; Janus Kinase Inhibitors; Pain; Patient Education as Topic; Peanut Hypersensitivity; Phosphodiesterase 4 Inhibitors; Sodium Hypochlorite

Atopic dermatitis is highly prevalent in black/African American, Asian, and Hispanic patients, making assessment of these populations in clinical trials important. Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate atopic dermatitis. In two pivotal phase III clinical trials in patients aged ≥ 2 years, crisaborole was superior to vehicle in reducing global disease severity. The most common treatment-related adverse event was application site pain.. The objective of this study was to investigate the efficacy and safety of crisaborole according to patient race and ethnicity.. A pooled post hoc analysis by race and ethnicity of the two pivotal trials and a safety extension trial was performed. Race included white or nonwhite (encompassing Asian/native Hawaiian/other Pacific Islander, black/African American, and other/American Indian/Alaskan native); ethnicity included Hispanic/Latino or not Hispanic/Latino.. In white, nonwhite, Hispanic/Latino, and not Hispanic/Latino groups at day 29, more crisaborole- than vehicle-treated patients achieved improvements in global disease severity [Investigator's Static Global Assessment of clear/almost clear with a ≥ 2-grade improvement (white: 33.5% vs. 22.3%, nominal p < 0.001; nonwhite: 30.0% vs. 21.3%, nominal p < 0.05; Hispanic/Latino: 35.4% vs. 18.2%, nominal p < 0.01; not Hispanic/Latino: 31.3% vs. 22.8%, nominal p < 0.01)]. Crisaborole treatment also improved atopic dermatitis signs/symptoms and quality of life. Frequency of crisaborole-related adverse events was 7.1-8.5% in the pivotal trials.. Across races and ethnicities, crisaborole demonstrated efficacy for the treatment of mild-to-moderate atopic dermatitis, with a low frequency of treatment-related adverse events.

Topics: Administration, Cutaneous; Adolescent; Adult; Aged; Boron Compounds; Bridged Bicyclo Compounds, Heterocyclic; Child; Child, Preschool; Dermatitis, Atopic; Dermatologic Agents; Ethnicity; Female; Health Status Disparities; Humans; Male; Middle Aged; Ointments; Pain; Pain Measurement; Quality of Life; Racial Groups; Severity of Illness Index; Skin; Time Factors; Treatment Outcome; Young Adult

Crisaborole, a phosphodiesterase 4 (PDE4) inhibitor, has been approved for the treatment of mild to moderate atopic dermatitis. Atopic dermatitis is often associated with increased pain. Using a mouse model, this study investigated whether crisaborole suppresses pain associated with atopic dermatitis and the potential mechanisms underlying it. The mouse model for atopic dermatitis was developed by repeatedly applying MC903. MC903-treated mice had increased spontaneous scratching (itch-related behaviour) and wiping behaviour (pain-related behaviour). Crisaborole was topically applied to the cheek skin of MC903-treated mice, and it reduced both itch- and pain-related behaviours in these mice. Immunofluorescence staining revealed that crisaborole reduced neutrophil infiltration and interaction of neutrophils with sensory neurones. Intradermal injection of S100A8/A9, proinflammatory neutrophil mediator, enhanced not only itch-related behaviours evoked by histamine or chloroquine, but also pain-related behaviours evoked by capsaicin. Calcium imaging of mouse dorsal root ganglion neurones revealed that pretreatment with S100A8/A9 significantly increased calcium responses to histamine and capsaicin, and the proportion of chloroquine-sensitive neurones. These findings suggest that the PDE4 inhibitor reduces itch and pain, in part by inhibiting infiltration of S100A8/A9-containing neutrophils in a mouse model of MC903-induced atopic dermatitis.

Topics: Animals; Calcium; Capsaicin; Chloroquine; Dermatitis, Atopic; Disease Models, Animal; Histamine; Neutrophil Infiltration; Pain; Pruritus

Topics: Administration, Cutaneous; Adolescent; Adult; Boron Compounds; Bridged Bicyclo Compounds, Heterocyclic; Child; Dermatitis, Atopic; Face; Female; Humans; Male; Middle Aged; Pain; Phosphodiesterase 4 Inhibitors; Retrospective Studies; Young Adult

Long-term topical treatment is often required for atopic dermatitis (AD), a chronic inflammatory skin disease.. To assess the long-term safety results from a multicenter, open-label, 48-week safety study (AD-303) of patients (N = 517) ≥2 years of age with mild to moderate AD who continued crisaborole treatment, a topical phosphodiesterase-4 inhibitor, after completing a 28-day phase 3 pivotal study (AD-301, AD-302).. Global disease severity was assessed in patients every 4 weeks, and if assessed as mild or greater, a 28-day treatment period with crisaborole applied twice daily was initiated. Adverse events (AEs), including treatment-emergent AEs (TEAEs), and serious AEs were analyzed.. During the pivotal studies and AD-303, 65% of patients reported ≥1 TEAE, most of which were mild (51.2%) or moderate (44.6%) and considered unrelated to treatment (93.1%). The frequency and severity of TEAEs were consistent. The most frequently reported treatment-related AEs (overall, 10.2%) were dermatitis atopic (3.1%), application-site pain (2.3%), and application-site infection (1.2%). Nine patients (1.7%) discontinued the long-term study because of TEAEs.. Long-term efficacy was not analyzed.. Crisaborole ointment had a low frequency of treatment-related AEs over 48 weeks of treatment of patients with AD.

Topics: Adolescent; Adult; Aged; Boron Compounds; Bridged Bicyclo Compounds, Heterocyclic; Child; Child, Preschool; Dermatitis, Atopic; Dermatologic Agents; Disease Progression; Female; Humans; Infections; Male; Middle Aged; Ointments; Pain; Phosphodiesterase 4 Inhibitors; Severity of Illness Index; Symptom Flare Up; Young Adult