Atopic dermatitis is a chronic, pruritic inflammatory dermatosis that affects up to 25% of children and 2% to 3% of adults. This guideline addresses important clinical questions that arise in atopic ...dermatitis management and care, providing recommendations based on the available evidence. In this third of 4 sections, treatment of atopic dermatitis with phototherapy and systemic immunomodulators, antimicrobials, and antihistamines is reviewed, including indications for use and the risk-benefit profile of each treatment option.
Background The ichthyoses are rare genetic disorders associated with generalized scaling, erythema, and epidermal barrier impairment. Pathogenesis-based therapy is largely lacking because the ...underlying molecular basis is poorly understood. Objective We sought to characterize molecularly cutaneous inflammation and its correlation with clinical and barrier characteristics. Methods We analyzed biopsy specimens from 21 genotyped patients with ichthyosis (congenital ichthyosiform erythroderma, n = 6; lamellar ichthyosis, n = 7; epidermolytic ichthyosis, n = 5; and Netherton syndrome, n = 3) using immunohistochemistry and RT-PCR and compared them with specimens from healthy control subjects, patients with atopic dermatitis (AD), and patients with psoriasis. Clinical measures included the Ichthyosis Area Severity Index (IASI), which integrates erythema (IASI-E) and scaling (IASI-S); transepidermal water loss; and pruritus. Results Ichthyosis samples showed increased epidermal hyperplasia (increased thickness and keratin 16 expression) and T-cell and dendritic cell infiltrates. Increases of general inflammatory (IL-2), innate (IL-1β), and some TH 1/interferon (IFN-γ) markers in patients with ichthyosis were comparable with those in patients with psoriasis or AD. TNF-α levels in patients with ichthyosis were increased only in those with Netherton syndrome but were much lower than in patients with psoriasis and those with AD. Expression of TH 2 cytokines (IL-13 and IL-31) was similar to that seen in control subjects. The striking induction of IL-17–related genes or markers synergistically induced by IL-17 and TNF-α (IL-17A/C, IL-19, CXCL1, PI3, CCL20, and IL36G; P < .05) in patients with ichthyosis was similar to that seen in patients with psoriasis. IASI and IASI-E scores strongly correlated with IL-17A ( r = 0.74, P < .001) and IL-17/TNF–synergistic/additive gene expression. These markers also significantly correlated with transepidermal water loss, suggesting a link between the barrier defect and inflammation in patients with ichthyosis. Conclusion Our data associate a shared TH 17/IL-23 immune fingerprint with the major orphan forms of ichthyosis and raise the possibility of IL-17–targeting strategies.
Background Additional topical treatments for atopic dermatitis (AD) are needed that provide relief while minimizing risks. Objective We sought to assess the efficacy and safety of crisaborole ...ointment, a phosphodiesterase 4 inhibitor, in two phase III AD studies (AD-301: NCT02118766 ; AD-302: NCT02118792 ). Methods Two identically designed, vehicle-controlled, double-blind studies enrolled and randomly assigned (2:1, crisaborole:vehicle) patients aged 2 years or older with an Investigator's Static Global Assessment (ISGA) score of mild or moderate for twice-daily application for 28 days. The primary end point was ISGA score at day 29 of clear (0)/almost clear (1) with 2-grade or greater improvement from baseline. Additional analyses included time to success in ISGA score, percentage of patients achieving clear/almost clear, reduction in severity of AD signs, and time to improvement in pruritus. Results More crisaborole- than vehicle-treated patients achieved ISGA score success (clear/almost clear with ≥2-grade improvement; AD-301: 32.8% vs 25.4%, P = .038; AD-302: 31.4% vs 18.0%, P < .001), with a greater percentage with clear/almost clear (51.7% vs 40.6%, P = .005; 48.5% vs 29.7%, P < .001). Crisaborole-treated patients achieved success in ISGA score and improvement in pruritus earlier than those treated with vehicle (both P ≤ .001). Treatment-related adverse events were infrequent and mild to moderate in severity. Limitations Short study duration was a limitation. Conclusions Crisaborole demonstrated a favorable safety profile and improvement in all measures of efficacy, including overall disease severity, pruritus, and other signs of AD.
Background There is a paucity of literature to direct physicians in the prescribing of immunomodulators for patients with severe atopic dermatitis (AD). Objective To survey systemic agent prescribing ...practices for severe childhood AD among clinicians in the United States and Canada. Methods The TREatment of severe Atopic dermatitis in children Taskforce (TREAT), US&CANADA, a project of the Pediatric Dermatology Research Alliance (PeDRA), developed an online multiple-response survey to assess clinical practice, gather demographic information and details of systemic agent selection, and identify barriers to their use in patients with recalcitrant pediatric AD. Results In total, 133 of 290 members (45.9%) of the Society for Pediatric Dermatology completed the survey, and 115 of 133 (86.5%) used systemic treatment for severe pediatric AD. First-line drugs of choice were cyclosporine (45.2%), methotrexate (29.6%), and mycophenolate mofetil (13.0%). The most commonly used second-line agents were methotrexate (31.3%) and mycophenolate mofetil (30.4%); azathioprine was the most commonly cited third-line agent. The main factors that discouraged use of systemic agents were side-effect profiles (82.6%) and perceived risks of long-term toxicity (81.7%). Limitations Investigation of the sequence of systemic medications or combination systemic therapy was limited. Recall bias may have affected the results. Conclusion Great variation exists in prescribing practices among American and Canadian physicians using systemic agents for treatment of pediatric AD.
Background Little is known about the epidemiology of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in children. Objective We sought to determine the morbidity, mortality, and ...comorbid health conditions of SJS and TEN in US children. Methods This was a cross-sectional study of the 2009 to 2012 Nationwide Inpatient Sample, which contains a representative 20% sample of all US hospitalizations. Sociodemographics, inflation-adjusted cost, length of stay, comorbidities, and mortality were analyzed using descriptive statistics and multivariate regression analyses. Results The incidences of SJS, SJS-TEN, and TEN were a mean 5.3, 0.8, and 0.4 cases per million children per year in the US, respectively. Prolonged length of stay and higher costs of care (SJS: 9.4 ± 0.6 days, $24,947 ± $3171; SJS-TEN: 15.7 ± 1.5 days, $63,787 ± $8014; TEN: 20.4 ± 6.3 days, $102,243 ± $37,588) were observed compared with all other admissions (4.6 ± 0.1 days, $10,496 ± $424). Mortality was 0% for SJS, 4% for SJS-TEN, and 16% for TEN. In regression models, predictors of mortality included renal failure (adjusted OR aOR 300.28, 95% confidence interval CI 48.59->999.99), malignancy (aOR 54.33, 95% CI 9.40-314.22), septicemia (aOR 30.45, 95% CI 7.91-117.19), bacterial infection (aOR 20.38, 95% CI 5.44-76.36), and epilepsy (aOR 5.56, 95% CI 1.37-26.2). Limitations Data regarding treatment were not available. Date of diagnosis of comorbidities was not present, precluding temporal analysis. Conclusions Pediatric SJS/TEN poses a substantial health burden in the United States.
Background The National Eczema Association has received increasing numbers of patient inquiries regarding “steroid addiction syndrome,” coinciding with the growing presence of social media dedicated ...to this topic. Although many of the side effects of topical corticosteroids (TCS) are addressed in guidelines, TCS addiction is not. Objective We sought to assess the current evidence regarding addiction/withdrawal. Methods We performed a systematic review of the current literature. Results Our initial search yielded 294 results with 34 studies meeting inclusion criteria. TCS withdrawal was reported mostly on the face and genital area (99.3%) of women (81.0%) primarily in the setting of long-term inappropriate use of potent TCS. Burning and stinging were the most frequently reported symptoms (65.5%) with erythema being the most common sign (92.3%). TCS withdrawal syndrome can be divided into papulopustular and erythematoedematous subtypes, with the latter presenting with more burning and edema. Limitations Low quality of evidence, variability in the extent of data, and the lack of studies with rigorous steroid addiction methodology are limitations. Conclusions TCS withdrawal is likely a distinct clinical adverse effect of TCS misuse. Patients and providers should be aware of its clinical presentation and risk factors.
Background There are no systemic therapies approved in the United States to treat pediatric psoriasis. Objective We sought to evaluate long-term safety and efficacy of etanercept in children and ...adolescents with moderate to severe plaque psoriasis. Methods This 5-year, open-label extension study enrolled patients aged 4 to 17 years who had participated in a 48-week parent study. End points included occurrence of adverse events (AEs) and serious AEs including infections, and rates of 75% and 90% improvement in Psoriasis Area and Severity Index score and clear/almost clear on static physician global assessment. Results Of 182 patients enrolled, 181 received etanercept and 69 completed 264 weeks. Through week 264, 161 (89.0%) patients reported an AE, most commonly upper respiratory tract infection (37.6%), nasopharyngitis (26.0%), and headache (21.5%). Seven patients reported 8 serious AEs; only 1 (cellulitis) was considered treatment-related. No cases of opportunistic infections or malignancy were reported. Rates of 75% improvement in Psoriasis Area and Severity Index score (∼60%–70%) and 90% improvement in Psoriasis Area and Severity Index score (∼30%–40%) and static physician global assessment status clear/almost clear (∼40%–50%) were maintained through week 264. Limitations The number of patients remaining on study at week 264 was small. Conclusion Etanercept in pediatric patients was generally well tolerated and efficacy was maintained in those who remained in the study for up to 264 weeks.
Children with atopic dermatitis (AD) experience significant sleep disruption, and clinically, the disease is noted to worsen in a circadian manner at night. Epidemiologic findings highlight many ...negative consequences of AD, such as impaired linear growth, which is uniquely related to disturbed sleep. Clinical guidelines currently recommend assessing sleep in patients with AD as a crucial parameter of disease control with appropriate treatment. In this review we describe our current understanding of the roles of sleep cycles and circadian rhythms in the nighttime exacerbation of AD (nocturnal eczema). We present a schematic to explain the mechanism of nocturnal eczema. Treatment options for sleep disturbance and future directions for research are discussed in the context of AD.
Background B cells undergo maturation and class-switching in response to antigen exposure and T-cell help. Early B-cell differentiation has not been defined in patients with early-onset atopic ...dermatitis (AD). Objective We sought to define the frequency of B-cell subsets associated with progressive B-cell maturation and IgE class-switching. Methods We studied 27 children and 34 adults with moderate-to-severe AD (mean SCORAD score, 55 and 65, respectively) and age-matched control subjects (15 children and 27 adults). IgD/CD27 and CD24/CD38 core gating systems and an 11-color flow cytometric panel were used to determine the frequencies of circulating B-cell subsets. Serum total and allergen-specific IgE (sIgE) levels were measured by using ImmunoCAP. Results Compared with adults, children showed T-cell predominance in the skin. Circulating CD19+ CD20+ B-cell counts were lower in patients with pediatric AD than in control subjects (24% vs 33%, P = .04), whereas CD3+ T-cell counts were higher (62% vs 52%, P = .05). A decreased B-cell/T-cell lymphocyte ratio with age was observed only in pediatric control subjects ( r = −0.48, P = .07). In pediatric patients with AD, a positive correlation was observed between B-cell/T-cell ratio and nonswitched memory B-cell counts ( r = 0.42, P = .03). Higher frequencies of positive sIgE levels were seen in pediatric patients with AD ( P < .0001). Diverse sIgE levels correlated with SCORAD scores and age of pediatric patients with AD ( P < .01). Positive correlations were observed between activated B-cell and memory T-cell counts ( P < .02). In patients with AD, IgE sensitization to most allergens clustered with age, TH 1, TH 2, total IgE levels, and B-cell memory subsets. Conclusions Peripheral B and T cells are altered in pediatric patients with early AD, but T cells predominate in skin lesions.
Objective To define the clinical spectrum of regional congenital anomalies associated with large cutaneous hemangiomas of the lower half of the body, clarify risk for underlying anomalies on the ...basis of hemangioma location, and provide imaging guidelines for evaluation. Study design We conducted a multi-institutional, retrospective case analysis of 24 new patients and review of 29 published cases. Results Hemangiomas in our series tended to be “segmental” and often “minimal growth” in morphology. Such lesions were often extensive, covering the entire leg. Extensive limb hemangiomas also showed potential for extracutaneous anomalies, including underlying arterial anomalies, limb underdevelopment, and ulceration. The cutaneous hemangioma and underlying anomalies demonstrated regional correlation. Myelopathies were the most common category of associated anomalies. Conclusions We propose the acronym “LUMBAR” to describe the association of Lower body hemangioma and other cutaneous defects, Urogenital anomalies, Ulceration, Myelopathy, Bony deformities, Anorectal malformations, Arterial anomalies, and Renal anomalies. There are many similarities between LUMBAR and PHACE syndrome, which might be considered regional variations of the same. Although guidelines for imaging are suggested, prospective studies will lead to precise imaging recommendations and help determine true incidence, risk and long-term outcomes.
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