Managing pediatric psoriasis: update on treatments and challenges-a review.

BACKGROUND: Psoriasis is a chronic, immune-mediated inflammatory disease with prominent cutaneous features, although the limited number of medications approved for pediatric psoriasis makes treating this population difficult. This review provides an overview of the challenges associated with diagnosing and treating pediatric psoriasis as well as the approved and off-label treatments for children and infants with psoriasis. METHODS: Articles relevant to pediatric psoriasis were identified using a series of PubMed searches. Topics relevant to pediatric psoriasis were explored, including disease characteristics, epidemiology, treatment efficacy and safety, and access to care. Publications previously known to the authors were also included. RESULTS: Clinical features of psoriasis can be challenging to identify clinically, and patients face challenges gaining access to treatment. Most medications that have been approved for adult psoriasis lack data and labeling to support safe and effective use in pediatric patients, and therefore access is limited. A growing number of clinical trials using biologic agents for pediatric psoriasis aim to broaden available treatment options but may also raise unique concerns associated with the use of these medications in children. CONCLUSION: Pediatric psoriasis is underrecognized and often undertreated. Clinicians must balance relative risks and potential benefits when developing a treatment strategy for these patients.

Development and validation of the Axillary Sweating Daily Diary: a patient-reported outcome measure to assess axillary sweating severity.

BACKGROUND: Hyperhidrosis is estimated to affect ~ 4.8% of the US population, and most patients experience a negative psychological impact. Here, we describe development and psychometric evaluation of a patient-reported outcome (PRO) measure to assess severity of axillary hyperhidrosis in clinical trials that meets current U.S. regulatory standards to support product approvals. METHODS: Three rounds of hybrid concept-elicitation/cognitive-debriefing qualitative interviews were conducted in adults with clinician-diagnosed primary axillary hyperhidrosis, followed by similar interviews in children/adolescents. The draft measure included diary items for presence, severity, impact and bothersomeness (basis of the Axillary Sweating Daily Diary [ASDD]), exploratory weekly impact items, and a single-item Patient Global Impression of Change (PGIC). Phase 2 (adults only) and phase 3 (adults and children ≥9 years) clinical trial data were utilized to evaluate measurement properties of the resulting draft measure: floor/ceiling effects, nonresponse bias, test-retest reliability, construct validity, and responsiveness were assessed. The primary concept of interest was axillary sweating severity (ASDD Item 2); however, additional supportive concepts were explored to allow for development of a comprehensive hyperhidrosis measure. RESULTS: Twenty-nine patient interviews were conducted (N = 21 adult and N = 8 children/adolescents), resulting in the ASDD (4 items, patients ≥16y) and child-specific ASDD-C (2 items ≥9y to <16y), as well as 6 Weekly Impact items and the PGIC (patients ≥16y). No floor/ceiling effects or response biases were identified. Consistency between hypothesized and observed correlation patterns between ASDD/ASDD-C items and other efficacy measures supported construct validity. Intraclass correlation coefficients supported test-retest reliability (0.91-0.93; Item 2). Large effect sizes (- 2.2 to - 2.4) demonstrated that the ASDD/ASDD-C Item 2 could detect changes in hyperhidrosis severity, supporting the measure's responsiveness. Patients perceiving a moderate improvement in symptoms on the PGIC experienced an average 3.8-point improvement on ASDD axillary sweating severity (Item 2); thus, a 4-point responder threshold was defined as a clinically meaningful change. CONCLUSIONS: Qualitative and quantitative evidence support the reliability and validity of the ASDD/ASDD-C and its use in the clinical evaluation of axillary hyperhidrosis treatments. Further evaluation of this measure in future research studies is warranted to demonstrate consistent performance across different axillary hyperhidrosis populations and in different study contexts.

Use of an alternative method to evaluate erythema severity in a clinical trial: difference in vehicle response with evaluation of baseline and postdose photographs for effect of oxymetazoline cream 1·0% for persistent erythema of rosacea in a phase IV study.

BACKGROUND: Once-daily topical oxymetazoline cream 1·0% significantly reduced persistent facial erythema of rosacea in trials requiring live, static patient assessments. OBJECTIVES: To evaluate critically the methodology of clinical trials that require live, static patient assessments by determining whether assessment of erythema is different when reference to the baseline photograph is allowed. METHODS: In two identically designed, randomized, phase III trials, adults with persistent facial erythema of rosacea applied oxymetazoline or vehicle once daily. This phase IV study evaluated standardized digital facial photographs from the phase III trials to record ≥ 1-grade Clinician Erythema Assessment (CEA) improvement at 1, 3, 6, 9 and 12 h postdose. RESULTS: Among 835 patients (oxymetazoline n = 415, vehicle n = 420), significantly greater proportions of patients treated with oxymetazoline vs. vehicle achieved ≥ 1-grade CEA improvement. For the comparison between phase IV study results and the original phase III analysis, when reference to baseline photographs was allowed while evaluating post-treatment photographs, the results for oxymetazoline were similar to results of the phase III trials (up to 85.7%), but a significantly lower proportion of vehicle recipients achieved ≥ 1-grade CEA improvement (up to 29.7% [phase 4] vs. 52.3% [phase 3]; P<0.001). In the phase IV study, up to 80·2% of patients treated with oxymetazoline achieved at least moderate erythema improvement vs. up to 22·9% of patients treated with vehicle. The association between patients' satisfaction with facial skin redness and percentage of erythema improvement was statistically significant. CONCLUSIONS: Assessment of study photographs, with comparison to baseline, confirmed significant erythema reduction with oxymetazoline on the first day of application. Compared with the phase III trial results, significantly fewer vehicle recipients attained ≥ 1-grade CEA improvement, suggesting a mitigated vehicle effect. This methodology may improve the accuracy of clinical trials evaluating erythema severity.

Report from the third international consensus meeting to harmonise core outcome measures for atopic eczema/dermatitis clinical trials (HOME).

This report provides a summary of the third meeting of the Harmonising Outcome Measures for Eczema (HOME) initiative held in San Diego, CA, U.S.A., 6-7 April 2013 (HOME III). The meeting addressed the four domains that had previously been agreed should be measured in every eczema clinical trial: clinical signs, patient-reported symptoms, long-term control and quality of life. Formal presentations and nominal group techniques were used at this working meeting, attended by 56 voting participants (31 of whom were dermatologists). Significant progress was made on the domain of clinical signs. Without reference to any named scales, it was agreed that the intensity and extent of erythema, excoriation, oedema/papulation and lichenification should be included in the core outcome measure for the scale to have content validity. The group then discussed a systematic review of all scales measuring the clinical signs of eczema and their measurement properties, followed by a consensus vote on which scale to recommend for inclusion in the core outcome set. Research into the remaining three domains was presented, followed by discussions. The symptoms group and quality of life groups need to systematically identify all available tools and rate the quality of the tools. A definition of long-term control is needed before progress can be made towards recommending a core outcome measure.

Addition of topical pimecrolimus to once-daily mid-potent steroid confers no short-term therapeutic benefit in the treatment of severe atopic dermatitis; a randomized controlled trial.

BACKGROUND: Combination therapy with pimecrolimus cream 1%, a topical calcineurin inhibitor (TCI), and fluticasone propionate cream 0.05% (FP), a mid-potency topical corticosteroid, may have a synergistic effect for treatment of atopic dermatitis (AD) because their mechanism of action differs. OBJECTIVES: To assess the efficacy of concomitant pimecrolimus twice daily/FP once daily vs. vehicle twice daily/FP once daily in patients with severe AD. METHODS: An exploratory, 2-week, double-blind, randomized, within-patient study was conducted (n = 45). Two target areas of similar severity, size and location were assessed. Assessments included the modified Eczema Area and Severity Index (0-12 scale) (primary variable), localized investigator global assessment (0-4 scale) and Patients' Self-Assessment of Disease Severity (0-4 scale). RESULTS: Data for all variables were similar for the TCI/FP and vehicle/FP treatments. CONCLUSIONS: The efficacy observed for treatment of severe AD flares with this TCI/FP combination regimen was equivalent to that of vehicle/FP.

Safety of fluticasone propionate cream 0.05% for the treatment of severe and extensive atopic dermatitis in children as young as 3 months.

BACKGROUND: Topical corticosteroids are useful for the treatment of pediatric dermatoses. However, concerns regarding possible systemic and topical toxicities have limited the use of moderate-potency corticosteroids in children. OBJECTIVE: Our purpose was to characterize the safety of fluticasone propionate cream in children. METHODS: Children between 3 months and 5 years 11 months (n = 32) and 3 up to 6 years of age (n = 19) with moderate to severe atopic dermatitis (> or =35% body surface area; mean body surface area treated, 64%) were treated with fluticasone propionate cream, 0.05% twice daily for 3 to 4 weeks. Serum cortisol response, fluticasone levels, skin changes, and adverse events were analyzed. RESULTS: Mean cortisol levels were similar at baseline (13.76 +/- 6.94 microg/dL prestimulation and 30.53 +/- 7.23 microg/dL poststimulation) and at end of treatment (12.32 +/- 6.92 microg/dL prestimulation and 28.84 +/- 7.16 microg/dL poststimulation). Only 2 of 43 children had end-treatment poststimulation values less than 18.0 microg/dL. No significant adverse cutaneous effects were noted. CONCLUSION: Fluticasone propionate cream 0.05% appears to be safe for the treatment of severe eczema for up to 4 weeks in children 3 months of age and older.

Cutaneous reactions to anticonvulsant medications.

Skin eruptions are an important consideration for any clinician who prescribes anticonvulsant medications. The timely recognition and accurate diagnosis of cutaneous reactions can prevent potentially fatal reactions and affect subsequent anticonvulsant treatment options. This review addresses the most common and most serious cutaneous reactions to anticonvulsant medications. The anticonvulsant hypersensitivity syndrome and individual antiepileptic medications that cause severe skin reactions will be reviewed. These reactions include morbilliform and urticarial drug eruptions as well as the erythema multiforme spectrum.

Stevens-Johnson syndrome caused by the antiretroviral drug nevirapine.

Nevirapine is a non-nucleoside reverse transcriptase inhibitor widely used in combination with other antiretroviral agents for the treatment of HIV infection. Severe rash, including the Stevens-Johnson syndrome (SJS), is the major toxicity of nevirapine and is described in the package labeling with a prominent, boxed warning. Though physicians treating large populations of patients with HIV are well aware of this complication, only one other report of nevirapine-associated SJS has been documented in the dermatology literature. We describe 2 cases of SJS related to nevirapine use and review the literature on this newly recognized association.

Pimecrolimus cream 1%: a new development in nonsteroid topical treatment of inflammatory skin diseases.

Atopic dermatitis (AD) is one of a family of inflammatory skin diseases (psoriasis, irritant contact dermatitis, and allergic contact dermatitis). Dermal inflammation and production of proinflammatory cytokines by activated T cells is a prominent and defining characteristic in all of these conditions. Corticosteroids, though effective and potent immunosuppressants, are associated with a number of systemic and local adverse effects. The ascomycin derivative pimecrolimus (formerly ASM 981) is a nonsteroid with topical anti-inflammatory activity. Pimecrolimus cream 1% is minimally absorbed into the circulation; thus, it has a low bioavailability-reducing the risk for systemic adverse effects. The efficacy and safety of pimecrolimus cream 1% has been well shown in diverse patient populations with inflammatory skin diseases in several well-controlled trials. Significant and rapid amelioration of the signs and symptoms of AD was established in 3 studies lasting 6 weeks each, evaluating 589 pediatric patients. In a 1-year study, pimecrolimus was applied at the first signs and symptoms of eczema to prevent the progression of AD to flares. Flares were prevented in over 50% of patients who used pimecrolimus cream 1%, reducing or completely eliminating the need for topical corticosteroids during a 1-year treatment period. Results in pimecrolimus studies in chronic irritant hand dermatitis and chronic hand dermatitis of mixed causes indicate potential for use in these important diseases, and further study in these indications is warranted.

Topical therapies and medications in the pediatric patient.

Topical medications and therapies are necessary for the proper management of skin diseases in children; however, physicians must be aware of the differences in percutaneous absorption and the risks for toxicity from topical medications, which are often unique to infants and children. Topical therapy must be individualized, and success often depends on proper vehicle selection, ease of application, and cost to patients and their families. Although many commercially available topical therapies are not FDA approved for use in children, recently enacted legislation has served to stimulate much-needed drug research in pediatric patients. New therapies on the horizon, such as tacrolimus, may prove to be equally efficacious and less toxic.

Benign cutaneous vascular tumors of infancy: when to worry, what to do.

OBJECTIVES: To discuss the current knowledge regarding complicated hemangiomas (cervicofacial, periorbital, lumbosacral, and parotid), including the associated syndromes of diffuse neonatal hemangiomatosis and PHACES (posterior fossa malformations, most commonly of the Dandy-Walker variant; hemangiomas [especially large, plaquelike, facial lesions]; arterial anomalies; cardiac anomalies and coarctation of the aorta; eye abnormalities; and sternal cleft and/or supraumbilical raphe). To discuss 2 newly recognized entities that may be a source of diagnostic confusion with the common hemangioma, the kaposiform hemangioendothelioma and tufted angioma. To discuss the risks and benefits of current treatment options, including the use of systemic corticosteroids and interferon in necessary situations. DATA SOURCES: The pertinent world literature was reviewed and incorporated into experience from our pediatric dermatology practice at the University of Texas Medical School at Houston. CONCLUSIONS: The common hemangioma, kaposiform hemangioendothelioma, and tufted angioma, though benign histologically, may cause serious consequences for children. Dermatologists should be able to recognize unique clinical presentations of these lesions and obtain further diagnostic evaluation accordingly. Dermatologists should also be aware of available treatment options, including the use of systemic chemotherapy in life-threatening situations.

Pediatric photosensitivity disorders.

Physicians who serve the pediatric population are the first line in identification and management of photosensitivity disorders present in childhood. The role of the dermatologist is not only to identify and treat these disorders, but also to counsel patients and their families in specific light avoidance, photoprotection, and in some cases, major lifestyle adjusts. This article reviews photosensitivity disorders, treatment, and prevention.

A randomized trial to assess once-daily topical treatment of tinea corporis with butenafine, a new antifungal agent.

BACKGROUND: Tinea corporis treatment usually requires topical application of an antifungal agent for 2 to 3 weeks. OBJECTIVE: We evaluated short-term treatment of tinea corporis with butenafine hydrochloride, a new benzylamine with in vitro fungicidal activity. METHODS: Patients (n = 78) were randomly selected to apply butenafine or its cream vehicle alone once daily for 14 days and were periodically assessed until day 42. RESULTS: Butenafine recipients had significantly higher rates of mycologic cure beginning at day 7 (64% vs 9%) with continued improvements through day 42 (88% vs 17%). They also had higher rates of effective treatment (mycologic cure and 90% to 100% symptom improvement) at day 7 (33% vs 0%) with increasing rates through day 42 (81% vs 14%). CONCLUSION: Butenafine provides rapid and persistent antifungal activity and symptom relief in patients with tinea corporis. Significant effects were observed within 7 days of therapy initiation, and increasing effectiveness was observed 4 weeks after therapy.

Insect repellents: an overview.

The optimal management of arthropod bites is prevention, and many over-the-counter insect repellents are available. Since first marketed in 1956, deet has remained the most effective repellent against mosquitoes, biting fleas, gnats, and chiggers. Permethrin is applied to clothing rather than to skin, and it is a better repellent against ticks than deet. The risk of serious side effects with the use of deet is slight; nevertheless, the lowest effective concentration should be used. The current, popular repellent agents (for adults and children) and their active ingredients are discussed. In addition, the Environmental Protection Agency guidelines for the safe use of insect repellents are supplied.