Reliability and validity of the instrument for scoring clinical outcomes of research for epidermolysis bullosa (iscorEB).

BACKGROUND: Epidermolysis bullosa (EB) is a group of rare and currently incurable genetic blistering disorders. As more pathogenic-driven therapies are being developed, there is an important need for EB-specific validated outcomes measures designed for use in clinical trials. OBJECTIVES: To test the reliability and construct validity of an instrument for scoring clinical outcomes of research for EB (iscorEB), a new combined clinician- and patient-reported outcomes tool. METHODS: We conducted an observational study consisting of independent 1-day assessments (six assessors) at two academic hospitals. The assessments consisted of iscorEB clinician (iscorEB-c), Birmingham Epidermolysis Bullosa Severity (BEBS) and global severity assessment for physicians; and iscorEB patient (iscorEB-p), Quality of Life evaluation in Epidermolysis Bullosa and Children's Dermatology Life Quality Index for patients. Construct validity and intraclass correlation coefficients (ICCs) for interobserver, intraobserver and test-retest reliability were calculated. RESULTS: Overall, 31 patients with a mean age of 19·5 years (1·8-45·2) were included. Disease severity was mild in 42% of cases, moderate in 29% and severe in 29%. The interobserver ICC was 0·96 for both the clinician-reported section of iscorEB-c and BEBS. The ICC for intraobserver reliability was 0·91 and 0·70 for the skin and mucosal domains of iscorEB-c, respectively. Cronbach's alpha for iscorEB-c was 0·89. The test-retest reliability of iscorEB-p was 0·97 and Cronbach's alpha was 0·84. The clinical score differentiated between subjects with mild, moderate and severe disease, and both clinical and patient subscores discriminated between recessive dystrophic EB and other EB subtypes. CONCLUSIONS: iscorEB has robust reliability and construct validity, including strong ability to distinguish EB types and severities. Further studies are planned to test its responsiveness to change.

A randomized trial of the efficacy of a new micronized formulation versus a standard formulation of isotretinoin in patients with severe recalcitrant nodular acne.

BACKGROUND: Isotretinoin is very frequently the drug of choice for the management of severe recalcitrant nodular acne. Recently, a new micronized and more bioavailable formulation of isotretinoin has been developed that permits once-daily administration in lower doses than usually used with standard isotretinoin (Accutane), regardless of whether it is taken with or without food. OBJECTIVE: Our purpose was to determine whether micronized isotretinoin and standard isotretinoin are clinically equivalent. METHODS: In this multicenter, double-blind, double-dummy study, 600 patients with severe recalcitrant nodular acne were treated with either 0.4 mg/kg of micronized isotretinoin once daily without food (n = 300) or 1.0 mg/kg per day of standard isotretinoin in two divided doses with food (n = 300). Lesion counts were monitored over 20 weeks. RESULTS: Both treatment groups in this well-controlled clinical trial experienced an equivalent reduction in the number of total nodules (facial plus truncal). In addition, an equivalent proportion of patients achieved 90% clearance of the total number of nodules. Both formulations had similar results for other efficacy variables. CONCLUSION: Once-daily use of the micronized and more bioavailable formulation of isotretinoin under fasted conditions is clinically equivalent to the standard twice-daily formulation under fed conditions in the treatment of severe recalcitrant nodular acne.

Safety of a new micronized formulation of isotretinoin in patients with severe recalcitrant nodular acne: A randomized trial comparing micronized isotretinoin with standard isotretinoin.

BACKGROUND: Isotretinoin is a very effective drug for treating severe recalcitrant nodular acne. A new micronized formulation of isotretinoin has been shown to be clinically equivalent to standard isotretinoin with improved bioavailability and minimal food effect. The safety profile of the micronized formulation has not been described previously. OBJECTIVE: The objective of this article is to report the incidence and intensity of adverse events found in a comparative, double-blind efficacy study that showed clinical equivalence of the new micronized formulation of isotretinoin and the standard isotretinoin formulation (Accutane). METHODS: Six hundred patients with severe recalcitrant nodular acne were treated with micronized isotretinoin (n = 300) under fasted conditions or standard isotretinoin (n = 300) under fed conditions. One cohort received single daily doses of 0.4 mg/kg of micronized isotretinoin without food and the other cohort received 1.0 mg/kg per day of standard isotretinoin in two divided doses with food. Adverse events were monitored during 20 weeks of drug therapy. RESULTS: The proportion of adverse events in most body systems was generally lower in patients receiving micronized isotretinoin than in those receiving standard isotretinoin. CONCLUSION: Micronized isotretinoin appears to have a safety profile similar to that of standard isotretinoin and to carry a lower risk of mucocutaneous events and hypertriglyceridemia.

Black spot poison ivy: A report of 5 cases and a review of the literature.

Black-spot poison ivy dermatitis is a rare manifestation of a common condition. It occurs on exposure to the resins of the plants of the Rhus family also known as Toxicodendron. We describe 5 patients with black deposits on their skin and clothing after contact with poison ivy and review the literature reflecting different aspects of this phenomenon including clinical presentation, histologic findings, and historical background.

Managing adolescent acne.

Acne vulgaris, more commonly termed acne, is the most common skin disease treated by physicians. It affects an estimated 17 million people in the United States, including 85% or more of adolescents and young adults. Acne is a chronic condition that may last for years and cause emotional distress and permanent scarring. Although there is no cure, medications can control the disease and limit or prevent scar formation.

Epidermolysis bullosa with congenital pyloric atresia: novel mutations in the beta 4 integrin gene (ITGB4) and genotype/phenotype correlations.

Epidermolysis bullosa with pyloric atresia (EB-PA: OMIM 226730), also known as Carmi syndrome, is a rare autosomal recessive genodermatosis that manifests with neonatal mucocutaneous fragility associated with congenital pyloric atresia. The disease is frequently lethal within the first year, but nonlethal cases have been reported. Mutations in the genes encoding subunit polypeptides of the alpha 6 beta 4 integrin (ITGA6 and ITGB4) have been demonstrated in EB-PA patients. To extend the repertoire of mutations and to identify genotype-phenotype correlations, we examined seven new EB-PA families, four with lethal and three with nonlethal disease variants. DNA from patients was screened for mutations using heteroduplex analysis followed by nucleotide sequencing of PCR products spanning all beta 4 integrin-coding sequences. Mutation analysis disclosed 12 distinct mutations, 11 of them novel. Four mutations predicted a premature termination codon as a result of nonsense mutations or small out-of-frame insertions or deletions, whereas seven were missense mutations. This brings the total number of distinct ITGB4 mutations to 33. The mutation database indicates that premature termination codons are associated predominantly with the lethal EB-PA variants, whereas missense mutations are more prevalent in nonlethal forms. However, the consequences of the missense mutations are position dependent, and substitutions of highly conserved amino acids may have lethal consequences. In general, indirect immunofluorescence studies of affected skin revealed negative staining for beta 4 integrin in lethal cases and positive, but attenuated, staining in nonlethal cases and correlated with clinical phenotype. The data on specific mutations in EB-PA patients allows prenatal testing and preimplantation genetic diagnosis in families at risk.

A center's callosities.

We present a case report of a 14-year-old white male who developed hyperkeratotic plaques on the distal aspects of 2 toes. He was referred by his primary care physician for the treatment of onychomycosis. With questioning, the patient stated that he played center for his high school basketball team. After physical examination, he was diagnosed with callosities caused by his basketball activities. Proper nail hygiene and wearing of larger footwear resulted in improvement of his callosities. Sports-related cutaneous injuries should be included in the differential diagnosis of nail and toe abnormalities.

Avian mite bites acquired from a new source--pet gerbils: report of 2 cases and review of the literature.

BACKGROUND: Cutaneous manifestations of avian mite bites are not well recognized by physicians or patients. Clinical signs and symptoms are usually caused by bites from avian mites that have infested domestic poultry or birds nesting in or near human habitation. This report details 2 cases of pruritic papules acquired from avian mites that had infested pet gerbils and reviews the dermatologic literature about avian mites. OBSERVATIONS: An 11-year-old boy and an unrelated 10-year-old girl each had mysterious, pruritic papules for many months before their pet gerbils were found to be infested with Ornithonyssus sylviarum (the northern fowl mite) and Dermanyssus gallinae (the chicken mite), respectively. Symptoms resolved when the gerbils were removed from the home. CONCLUSIONS: Because infestation of pet gerbils with avian mites has never been reported, cases of avian mite bites and dermatitis may have gone unrecognized or misdiagnosed. Inquiry about ownership of pet gerbils may be helpful in patients with mysterious bites.

Long-term safety and efficacy of tacrolimus ointment for the treatment of atopic dermatitis in children.

Tacrolimus ointment is a nonsteroidal topical immunomodulator that was formulated specifically for the treatment of atopic dermatitis. A total of 255 children, 2 to 15 years of age, with moderate to severe atopic dermatitis applied 0.1% tacrolimus ointment twice daily for up to 12 months to assess long-term safety and efficacy. Patients on average were treated with tacrolimus ointment for 279 days or 87% of study days. Substantial improvements in the signs and symptoms of atopic dermatitis, percent body surface area affected, and the patient's or parent's assessment of pruritus were observed during the first week of treatment and were maintained throughout the study. Transient skin burning and itching were the most common drug application site adverse events. Occurrence of these symptoms decreased after the first few days of treatment. There was no increased incidence of infections or other significant adverse events. Effectiveness of tacrolimus was maintained with prolonged daily use. Tacrolimus ointment (0.1%) is safe and effective for long-term treatment of atopic dermatitis in children.

The prevalence of upper lip hair in black and white girls during puberty: a new standard.

In order to develop standards for upper lip hair in adolescent girls, 4693 observations in 856 black and white subjects were made over 9 years. Up to 2 years after menarche, 90% of girls had no upper lip hair. More than 2 years after menarche, 48.8% of black girls and 9.0% of white girls had small amounts of upper lip hair. This may be more significant in adolescent girls than in older women.

Estradiol and testosterone effects on lipids in black and white boys aged 10 to 15 years.

Previous studies of lipids in adolescent males have shown greater increases in triglycerides and decreases in high-density lipoprotein cholesterol (HDL-C) in white boys compared with black boys, significant correlations between sex hormones and lipids, and complex body mass index (BMI) hormone-lipid associations. Within this frame of reference, we assessed race, BMI, and sex hormones as predictors of lipid parameters in 536 black and white boys recruited from area schools. Black boys were more advanced in puberty than white boys. After adjusting for pubertal stage, estradiol (E2) levels were higher in black boys but free testosterone (T) levels did not differ. Age, pubertal stage, race, BMI, free T, and E2 were entered as explanatory variables for lipids in backward stepwise regression analyses. The BMI and race were retained in every model. Black boys had lower triglycerides and apolipoprotein B (apo B) and higher HDL-C. E2 was inversely associated with total cholesterol (TC), triglycerides, low-density lipoprotein cholesterol (LDL-C), apo B, and the LDL-C/HDL-C ratio. Free T was inversely associated with HDL-C and positively associated with apo B. Given the increases in free T and E2 during adolescence and the association of these hormones with both atherogenic and protective lipid parameters, racial differences in E2 could contribute to the more atherogenic lipid profile found in white boys after puberty.

Acquired port-wine stains and antecedent trauma: case report and review of the literature.

BACKGROUND: While cases of congenital port-wine stains (PWSs) are relatively common, cases of acquired PWSs are quite rare. Many of the reported cases of the acquired type have been reported to be related to previous trauma. OBSERVATIONS: We encountered a case of acquired PWSs in a 3-year-old girl. Her parents noted that the lesions appeared in areas of antecedent trauma. This prompted us to review all reported cases of acquired PWSs and to assess the relationship to trauma. Among the 59 cases reported, there was a slight female predominance (female-male ratio, 35:24). Seventeen (29%) of the cases were related to trauma. One report evaluated the effectiveness of lasers in the treatment of acquired PWSs and found that 54% of patients treated with pulsed dye lasers had an excellent response or complete clearance. CONCLUSIONS: Port-wine stains are not only congenital but can be acquired as well. Trauma can be one of the causes of acquired PWSs. To explain this phenomenon, various theories, including abnormal vascular repair and altered vascular innervation, have been proposed. Lasers are the treatment of choice in all cases of PWSs and may be more effective in those that are acquired.

Colocalization of alopecia areata and vitiligo.

We report an 18-year-old woman who had a 4-month history of colocalization of alopecia areata and vitiligo, principally on the occipital portion of the scalp.

Tinea pedis in children presenting as unilateral inflammatory lesions of the sole.

Tinea pedis is uncommon in prepubescent children and therefore the diagnosis may be difficult to make. We report tinea pedis in five children presenting as unilateral inflammatory lesions of the sole which was not readily diagnosed. The pathogen in all of our cases was Trichophyton rubrum.

Sex hormones and lipoproteins in adolescent male offspring of parents with premature coronary heart disease and a control group.

OBJECTIVE: To compare pubertal maturation, sex steroid hormones, and lipoproteins and their interrelationships in male offspring of parents with premature coronary heart disease (cases) and a control group. DESIGN: This was a cross-sectional comparison of cases and members of a control group 10 to 15 years of age. SUBJECTS AND METHODS: Offspring were recruited from patient lists of area physicians. Members of the control group were recruited from area schools. Body mass (kg/m2), serum lipids, lipoproteins, apolipoproteins, estradiol, and free testosterone were measured. RESULTS: Differences in age were not significant, but offspring were taller, heavier, and more mature. Offspring had higher total and low density lipoprotein cholesterol. Offspring had lower estradiol levels in early puberty but higher levels in late puberty. With family history and body mass in the regression models for lipid parameters, free testosterone was a significant explanatory factor for total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein, and estradiol was a significant predictor for apolipoprotein B. The percent of the variance in the lipid parameters explained by testosterone and estradiol was small. CONCLUSION: Sex hormone concentrations appear to be modest but significant predictors of lipoprotein and apolipoprotein concentrations in offspring and a control group in cross-sectional analysis. After controlling for pubertal maturation, hormone and lipid concentrations differed in offspring and the control group.

Milia en plaque of the eyelids in childhood: case report and review of the literature.

Milia en plaque is a rare type of primary milia. Most of the reported cases have occurred around the ears in adults. We report milia en plaque in a 10-year-old girl who presented with symmetrical erythematous plaques studded with milia on the eyelids. Histopathology revealed milia surrounded by a dense lymphocytic infiltrate. Administration of minocycline and manual expression of the milia successfully treated this condition.

A review of infantile and pediatric acne.

Acne occurs primarily in the first year of life and at puberty. Neonatal and infantile acne may reflect the relatively high androgens from the adrenal in girls and the adrenal and testes in boys characteristic of this age. Early in puberty, acne in boys and girls is primarily comedonal and midfacial. The best predictors of severe acne are early onset of comedones and serum levels of dehydroepiandrosterone sulfate. Early recognition and therapy of acne may prevent scarring and psychological stress.

Comparative efficacy and safety of two 0.025% tretinoin gels: results from a multicenter double-blind, parallel study.

BACKGROUND: The addition of polyolprepolymer-2 in tretinoin formulations may reduce tretinoin-induced cutaneous irritation. OBJECTIVE: This study compared the efficacy and safety of a new 0.025% tretinoin gel containing polyolprepolymer-2, its vehicle, and a commercially-available 0.025% tretinoin gel in patients with mild to moderate acne vulgaris. METHODS: In this 12-week multicenter, double-blind, parallel group study, efficacy was evaluated by objective lesion counts and the investigators' global evaluations. Subjective assessment of cutaneous irritation by the investigators and patients evaluated safety. RESULTS: The efficacy of the two active treatments in this 215 patient study was comparable, and both treatments were statistically significantly more effective than vehicle. When compared with the commercially-available tretinoin gel, the formulation containing polyolprepolymer-2 demonstrated statistically significantly less peeling at days 28, 56, and 84, statistically significantly less dryness by day 84, and statistically significantly less itching at day 14. Irritation scores for the formulation containing polyolprepolymer-2 were numerically lower but not statistically different from those of the commercially-available gel for erythema and burning. The number of cutaneous and noncutaneous adverse events were similar for both active medications. CONCLUSION: The two 0.025% gels studied demonstrated comparable efficacy. However, the gel formulation containing polyolprepolymer-2 caused significantly less peeling and drying than the commercially-available formulation by day 84 of the study.