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.

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.

Bowel-bypass syndrome without bowel bypass. Bowel-associated dermatosis-arthritis syndrome.

A recurrent, episodic illness that occurs in as many as 20% of patients who undergo ileojejunal bypass surgery for morbid obesity has been well characterized and includes inflammatory cutaneous lesions with a histologic appearance like that of neutrophilic vasculitis, a nondeforming polyarthritis, and other systemic manifestations. Current concepts of pathogenesis center on overgrowth of bacterial flora in the bypassed bowel segment with subsequent development of a circulating immune complex disease. We report, for the first time to our knowledge, an identical clinicopathologic syndrome in four patients who have not had jejunoileal bypass surgery. Each patient, however, had other gastrointestinal disease that we believe predisposed to this syndrome, possibly via circulating immune complexes with bowel-associated antigens. We propose the expanded term, bowel-associated dermatosis-arthritis syndrome, to incorporate these new cases. We believe that this is not a rare syndrome and that it is easily distinguishable from other types of cutaneous necrotizing vasculitis.

Concanavalin A distinguishes among diseases of altered epidermal differentiation.

Mannose-containing of glycoproteins from lesional tissue of several diseases of aberrant epidermal differentiation (palmar-plantar keratoderma, pachyonychia congenita, psoriasis, and epidermolytic hyperkeratosis) were analyzed by overlaying iodinated concanavalin A onto molecules separated by polyacrylamide gel electrophoresis. Gel autoradiograms showed that biopsy samples from patients with the same disease were very similar. The radioactivity profiles were different for each disease and were distinguishable from each other and from normal epidermis and callus. The resolution and sensitivity of this technique may be of diagnostic significance.

Uncombable hair (pili trianguli et canaliculi): evidence for dominant inheritance with complete penetrance based on scanning electron microscopy.

Uncombable or spun-glass hair (pili trianguli et canaliculi) is an uncommon condition in which the hair is "unmanageable" and has a distinct appearance on scanning electron microscopy. The hair is usually grossly abnormal in infancy and childhood, but may become normal later in life. Although dominant inheritance has been observed, most cases have been sporadic. Both recessive and dominant transmission with incomplete penetrance have been suggested as modes of inheritance. We report the occurrence of this condition in a young girl, her brother, and her father. Although the proposita and her brother had characteristically uncombable hair, their father appeared normal and denied any history of hair abnormality. However, the characteristic hair morphology was observed on scanning electron microscopy in all 3 relatives, documenting dominant transmission and complete penetrance of the gene in this family.

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.

Comparative safety and efficacy of clarithromycin and cefadroxil suspensions in the treatment of mild to moderate skin and skin structure infections in children.

A prospective, randomized, single (investigator) blind multicenter study was performed to compare the safety and efficacy of clarithromycin and cefadroxil oral suspensions in the treatment of mild to moderate skin and skin structure infections in children. Male and female patients ages 6 months to 12 years were enrolled at 24 study centers in the United States. Patients had signs and symptoms consistent with mild to moderate skin or skin structure infections judged suitable for oral antimicrobial therapy. Clarithromycin oral suspension was given to 118 children in a dose of 7.5 mg/kg (maximum of 500 mg) twice daily; cefadroxil oral suspension was given to 113 children in a dose of 15 mg/kg (maximum of 1000 mg) twice daily. Among clinically evaluable patients clinical success rates (cure plus improvement) were 96% (71 of 74) for clarithromycin and 98% (83 of 85) for cefadroxil (P = 0.664). Bacteriologic cure rates in evaluable clarithromycin and cefadroxil patients were 96% (72 of 75) and 99% (89 of 90), respectively (P = 0.331). Pathogen eradication rates based on 204 evaluable pathogens were 97% in the clarithromycin group and 99% in the cefadroxil group (P = 0.326). Adverse events were mild or moderate and were reported in 25% of clarithromycin and 35% of cefadroxil patients (P = 0.085). In both groups adverse events involved primarily the digestive tract. No significant laboratory changes were noted. Clarithromycin oral suspension appears to be a safe and effective alternative to cefadroxil for the treatment of pediatric skin and skin structure infections.

The relationship between skin maturation and electrical skin impedance.

When performing electrophysiological testing, high electrical impedance values are sometimes found in neonates. Since excessive impedance can invalidate test results, a study was conducted to delineate the relationship between skin maturation and electrical skin impedance. This study investigated the skin impedance in 72 infants ranging from 196 to 640 days of age from conception. Regression analyses demonstrated a significant relationship between impedance and age, with the highest impedance centered around full-term gestation with values falling precipitously at time points on either side. Clinically, impedance values fall to normal levels at approximately four months following full-term gestation. Skin impedance values are low in premature infants, but rapidly increase as the age approaches that of full-term neonates. Low impedance values in premature infants are attributed to greater skin hydration which results from immature skin conditions such as 1) thinner epidermal layers particularly at the transitional and cornified layers; 2) more blood flow to the skin; and 3) higher percentage of water composition. These factors facilitate the diffusion of water vapor through the skin. As the physical barrier to skin water loss matures with gestational age, the skin impedance reaches a maximum value at full term neonatal age. After this peak, a statistically significant inverse relationship exists between electrical skin impedance and age in the first year of life. This drop in skin impedance is attributed to an increase in skin hydration as a result of the greater functional maturity of eccrine sweat glands.

Skin lesions of the spinal axis and spinal dysraphism. Fifteen cases and a review of the literature.

OBJECTIVE: To catalog the paraspinal skin lesions of early childhood that are associated with occult spinal dysraphism. RESEARCH DESIGN: Retrospective review of a series of patients. SETTING: Tertiary care referral center. PATIENTS: Fifteen patients who had significant paraspinal skin lesions were identified from the personal files of the authors who saw them. RESULTS: The skin lesions included various combinations of hyperpigmentation, hypopigmentation, hypertrichosis, acrochordons, dimples, lipomas, hemangiomas, or teratomas. Not all lesions were evaluated with the same tests, which included plain roentgenography, ultrasonography, myelography, computed tomography, and magnetic resonance imaging. Of the 15 patients, six had spinal anomalies, eight had no apparent spinal dysraphism, and one had insufficient results of the evaluation to assess the spinal column. CONCLUSIONS: Early recognition of paraspinal skin lesions is essential to prevent neurologic damage. Urinary or fecal incontinence, recurrent urinary infections, muscle atrophy, foot deformities, weakness, pain, or decreased sensation in the lower extremities may eventually develop in these patients. Magnetic resonance imaging appears to be the single best screening test for dysraphism.

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.

Sacral hemangiomas and multiple congenital abnormalities.

Five infants with sacral hemangiomas and a particular constellation of congenital abnormalities are described. Three of the five infants had an imperforate anus associated with a fistula. Three of the five had renal anomalies; four had bony abnormalities of the sacrum, and three of these also had a lipomeningomyelocele. Four had skin tags, three of which were in the genital and sacral areas. Two of the five also had abnormalities of the external genitalia. This constellation of defects associated with a sacral hemangioma has not been, to our knowledge, elaborated previously.

The CHILD syndrome. Histologic and ultrastructural studies.

A 4 1/2-month-old female infant had cutaneous and musculoskeletal changes consistent with the diagnosis of congenital hemidysplasia with ichthyosiform erythroderma and limb defects (CHILD) syndrome. This syndrome encompasses abnormalities of several organ systems, and its origins and pathogenesis are poorly understood. This report describes an additional patient with this uncommon syndrome and includes light and electron microscopic studies of her skin lesions. Our patient's clinical features of meningocele, Shone's syndrome, and the electron microscopic findings have not previously been described in the American literature (to our knowledge) in association with this syndrome.

Neonatal pemphigus foliaceus.

BACKGROUND: Pemphigus refers to a group of autoimmune blistering diseases of the skin. Of the two major types of pemphigus, pemphigus vulgaris and pemphigus foliaceus, only pemphigus vulgaris has been known to affect newborn infants via passive transfer of maternal IgG antibodies across the placenta. Although pemphigus foliaceus antibodies have also been shown to cross the placenta, never before has a newborn been clinically affected. We report the first of neonatal pemphigus foliaceus confirmed by both clinical presentation and immunofluorescence studies. OBSERVATIONS: The distinguishing factors in this case were high antibody titers by indirect immunofluorescence present in both the mother and her fetus (1:640 and 1:80, respectively). CONCLUSIONS: A threshold of fetal antibody titer ( > 1:40) may need to be surpassed before neonatal disease can occur in pemphigus foliaceus. The likelihood of reaching this threshold has been shown to be increased with higher maternal antibody titers. Thus, strict control of maternal pemphigus foliaceus should lower the incidence of placental antibody transfer and improve neonatal outcome.

Simultaneous occurrence of idiopathic lipemic tears and massive seborrhea.

A 42-year-old man had idiopathic lipemic tears and massive seborrhea. Recent investigations have shown that cholesterol and other lipids occasionally found in tears are produced by meibomian rather than lacrimal glands. The finding in this patient of hypersecretion by both sebaceous glands and meibomian glands, a sebaceous gland variant, suggests that a common mechanism may regulate secretory control of both of these glands.

Laboratory evaluation of the child with recalcitrant eczema.

This article discusses many of the more common diagnoses that should be considered when managing a child with nonresponsive excema. Some of these possible diagnoses are infectious and parasitic disorders, psoriasis, heritable disorders, Langerhans cell histiocytosis, and syndromes with altered immunity and eczematous skin changes. This overview of diagnostic and laboratory evaluations of the child with eczema who fails standard therapy is presented as a useful guide in evaluating these patients.

Bacterial and candidal cutaneous infections in the neonate.

The skin and oral cavity of the neonate are colonized by a variety of organisms during the first few days of life. Some of these organisms constitute normal flora, but others are true pathogens or are capable of pathogenicity when host or environmental factors are altered in their favor. Cutaneous bacterial and yeast infections that afflict the newborn are discussed in terms of clinical presentation, laboratory evaluation, and appropriate management.

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.

Peutz-Jeghers syndrome.

Peutz-Jeghers syndrome is inherited as an autosomal dominant trait with variable incomplete penetrance. Patients with Peutz-Jeghers syndrome characteristically have hamartomatous polyps throughout their entire gastrointestinal tract, particularly in the small bowel, and mucocutaneous hyperpigmentation involving the lips, oral cavity, and skin. Although the intestinal hamartomatous polyps have a lower incidence of malignant change in the gastrointestinal tract than do adenomatous polyps, recent information suggests that the overall neoplastic transformation from Peutz-Jeghers syndrome is not a rare event.