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Background: Itch is the most bothersome symptom reported by patients with psoriasis. Safe and effective treatments for psoriasis that also address itch are needed. Objectives: To report effects of roflumilast cream on itch-related outcomes from a Phase 2b trial. Methods: Adults with chronic plaque psoriasis were randomized to roflumilast 0.3%, roflumilast 0.15%, or vehicle once-daily for 12 weeks. Psoriasis severity was assessed via the Investigator Global Assessment (IGA; a 5-point scale assessing plaque thickening, scaling, and erythema ranging from 0 [clear] to 4 [severe]) and ≥ 2 on a modified Psoriasis Area and Severity Index (PASI-HD, which combines severity of lesions and area affected, ranging from 0 [no disease] to 72 [maximal disease], with the actual percentage of the anatomical area involved in those patients with < 10% of anatomical area involved [e.g., 0.1 for 1% to 0.9 for 9%]). Itch was evaluated via Worst Itch Numeric Rating Scale (WI-NRS), Psoriasis Symptom Diary (PSD) Items 1 (severity of itch) and 2 (bother of itch), and itch-related sleep loss NRS scores. Post hoc correlation analyses between WI-NRS and PASI, WI-NRS and itch-related sleep loss, and WI-NRS and DLQI were also performed. Results: Roflumilast-treated patients had significantly greater improvements than vehicle-treated patients in WI-NRS and PSD Items 1 and 2 beginning at Week 2 and in itch-related sleep loss Weeks 6 through 12. Among patients with baseline WI-NRS ≥ 6, significantly more patients achieved ≥ 4-point improvement with roflumilast than with vehicle as early as Week 2. Itch severity had low correlation with PASI while WI-NRS and IGA were not always aligned. Limitations: The first assessment was at 2 weeks, limiting the ability to assess early onset of itch response. Conclusion: Roflumilast cream improved itch and itch-related sleep loss associated with chronic plaque psoriasis. ClinicalTrials.gov identifier: NCT03638258. [ABSTRACT FROM AUTHOR]

Background: Most patients with chronic plaque psoriasis receive topical treatment; however, available options lack a balance of efficacy with long-term safety and tolerability. Roflumilast cream 0.3% is a highly potent phosphodiesterase 4 (PDE4) inhibitor approved by the US FDA for treatment of psoriasis. Objective: The aim of this study was to define the pharmacokinetic (PK) profile of roflumilast delivered topically from a phase I maximal usage study and data from phase II and phase III studies. Methods: PK data for roflumilast and the active metabolite, roflumilast N-oxide, were determined from a phase I PK and safety maximal usage study of roflumilast cream 0.3% applied once daily for 14 days in patients with plaque psoriasis affecting body surface area (BSA) ≥20% (N = 26). Serial plasma samples were obtained on Days 1 and 15 to determine maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC). Plasma concentrations were also assessed at Weeks 3, 4, and 5 for terminal half-life (t½). Concentrations of roflumilast and roflumilast N-oxide in skin were assessed at Day 28 for 14 patients with psoriasis in a phase I/IIa study of once-daily roflumilast cream 0.5% and 0.15% for 28 days. Systemic exposure (Ctrough and AUC) of roflumilast and roflumilast N-oxide in two phase III trials (DERMIS-1, n = 245; DERMIS-2, n = 250) of roflumilast cream 0.3% for 8 weeks was assessed at Weeks 4 and 8. Results: Bioavailability of roflumilast cream 0.3% after topical administration was 1.5%. Unlike after oral dosing, the plasma concentration-time curve was flat, with a peak-to-trough ratio of 1.2. Roflumilast N-oxide concentrations were eightfold higher than roflumilast concentrations. The t½ in adult patients was 4.0 days for roflumilast and 4.6 days for roflumilast N-oxide following the last dose administered. Steady state was reached by Day 15. Concentrations of roflumilast in skin were, on average, 126- and 61.8-fold higher than corresponding mean plasma Ctrough following administration of roflumilast cream 0.15% and 0.5% daily for 28 days. Roflumilast N-oxide was quantifiable in only one skin sample (N = 27). Following 8 weeks of treatment in DERMIS-1, mean plasma Ctrough of roflumilast was 1.78 ng/mL, and 9.86 ng/mL for roflumilast N-oxide. In DERMIS-2, mean plasma Ctrough was 1.72 ng/mL and 10.2 ng/mL, respectively. In the maximal usage study (mean BSA: 27.5%), eight patients (30.8%) experienced adverse events (AEs) and all were mild or moderate, with no reports of diarrhea, headache, insomnia, or application-site pain; no patients discontinued treatment due to an AE. Conclusion: Topical administration of roflumilast cream 0.3% results in concentrations in skin 126- and 61.8-fold higher relative to plasma, which are much higher than expected to be achievable with oral dosing. PDE4 inhibition in the skin is likely due to roflumilast as compared with its active metabolite, as there is no significant conversion to roflumilast N-oxide in the skin. Consistent with reservoir formation and retention of drug in the stratum corneum, roflumilast is slowly released from the skin (t½ 4 days) and peak-to-trough ratio is 1.2. ClinicalTrials.gov Identifiers: NCT04279119, NCT03392168, NCT04211363, NCT04211389. [ABSTRACT FROM AUTHOR]

Introduction Roflumilast is a selective, highly potent phosphodiesterase 4 inhibitor under investigation as a nonsteroidal, once-daily cream for treatment of atopic dermatitis (AD). Methods We present pooled results from two identical phase 3 randomized controlled trials (INTEGUMENT-1: NCT04773587; INTEGUMENT-2: NCT04773600) of roflumilast cream 0.15%. Patients aged ≥6 years with mild to moderate AD were randomized 2:1 to apply roflumilast (n=884) or vehicle (n=453) cream once-daily for 4 weeks. The primary endpoint was validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) Success (Clear/Almost Clear vIGA-AD plus ≥2-grade improvement from baseline) at Week 4. Patient-reported outcomes (PROs) were evaluated using the Worst Itch-Numeric Rating Scale (WI-NRS), SCORing AD (SCORAD), Patient-Oriented Eczema Measure, Dermatology Life Quality Index/Children's Dermatology Life Quality Index, and the Dermatitis Family Impact questionnaire. Safety and tolerability were also evaluated. Results At Week 4, more roflumilast- than vehicle-treated patients achieved vIGA-AD Success (31.3% vs. 14.1%, P<0.0001), WI-NRS Success (≥4-point improvement on WI-NRS in patients aged ≥12 years with baseline WI-NRS ≥4; 31.9% vs. 16.6%, P<0.0001); and WI-NRS of 0/1 (in patients with baseline WI-NRS ≥2; 28.8% vs 18.5%, P=0.0087). At Week 4, roflumilast-treated patients improved more than vehicle-treated on the pruritus and sleep components of SCORAD (least squares mean percentage change −48.2% vs. −27.8%; [P<0.0001] and −47.9% vs. −22.9% [P<0.05], respectively). Differences favoring roflumilast were also seen for other secondary endpoints, including quality of life of the patient and family. Safety and local tolerability were favorable. Conclusion Once-daily, nonsteroidal roflumilast cream 0.15% improved PROs in patients with AD. [ABSTRACT FROM AUTHOR]

Background Roflumilast, a highly potent phosphodiesterase-4 inhibitor, is being investigated as a non-steroidal, once-daily cream for atopic dermatitis (AD). Methods INTEGUMENT-OLE (NCT04804605) was an open-label 52-week safety trial. Patients (N=658) with mild to moderate AD who completed a 4-week randomized vehicle-controlled phase 3 trial of roflumilast cream continued or switched to once-daily roflumilast cream 0.15% in this open-label extension trial. Starting at Week 4, patients achieving Validated Investigator Global Assessment for AD (vIGA-AD) score of 0 (Clear) switched to twice-weekly (BIW) maintenance dosing. The primary endpoint was safety; secondary endpoints included vIGA-AD, Worst Itch-Numeric Rating Scale (WI-NRS), and Eczema Area and Severity Index (EASI). "Disease control" was defined as duration of vIGA-AD=0/1 on BIW dosing following achievement of vIGA-AD=0. Results With cumulative treatment up to 56 weeks, 36.7% of patients reported treatment-emergent adverse events (AEs); most were mild to moderate in severity. Overall, 4.7% of patients had AEs deemed treatment-related and 3.0% discontinued due to AEs. The most common AEs (>2%) were COVID-19, upper respiratory tract infection, nasopharyngitis, and headache. At Week 52, 55.7%, 61.1%, and 53.6% of patients achieved vIGA-AD=0/1 (Clear/Almost Clear), ≥75% reduction in EASI, and ≥4-point reduction in WI-NRS (among patients aged ≥12 years with baseline WI-NRS ≥4), respectively. Of the 130 (19.8%) patients who achieved disease control, 50% maintained "disease control" for at least 281 days. Conclusion Treatment with roflumilast cream 0.15% demonstrated long-term safety in patients with AD consistent with parent trials and durable efficacy through 52 weeks, including patients who switched to BIW dosing. [ABSTRACT FROM AUTHOR]

Background Human CD200 receptor (CD200R, CD200R1), originally OX2R, is an inhibitory immune checkpoint receptor expressed on many myeloid cells, and lymphocyte populations including CD4 T and ILC2 cells, signaling via DOK2 and Erk/MAP kinases to inhibit the NFkB pathway and cytokine secretion. Its ligand, CD200, is expressed on the surface of tissues including endothelium, epithelia and neurons, where it moderates immune activation particularly at barrier sites including lung, skin and the GI tract. Published evidence, including GWAS studies, implicates dysregulation of the CD200 axis in many allergic, autoimmune and inflammatory diseases. Furthermore, a CD200R agonist antibody has demonstrated efficacy in an early phase clinical trial of moderate to severe atopic dermatitis patients. Methods We have engineered high affinity soluble CD200R agonists, comprising human CD200-Fc proteins with substantially increased (up to 130-fold) monomeric binding affinity for CD200R. Results High affinity human CD200-Fc a) out-performs wild type in inhibiting IL-6 release from a cell line expressing high levels of human CD200R, b) has superior potency to a CD200R agonist antibody in a humanized mouse model of contact hypersensitivity, and c) substantially reduces cell infiltrate in bronchoalveolar lavage fluid in a non-human primate model of airway inflammation. A high affinity murine CD200-Fc has been engineered for additional proof-of-concept studies, and is more potent than wild type in an in vivo model (collagen-induced arthritis). Finally, we describe ARQ-234, a high affinity CD200-Fc protein with antibody-like serum half-life in NHP, due to the introduction of mutations in the Fc domain which increase relative binding to the neonatal Fc receptor at low (endosomal) pH. ARQ-234 is currently in pre-clinical development as a therapeutic for atopic dermatitis. [ABSTRACT FROM AUTHOR]

In this post-hoc analysis, IGA clear or almost clear at week 6 was metby more patients treated with roflumilast than patients treated with vehicle (roflumilast 0.3%, 27.2%; roflumilast 0.15%, 22.3%; vehicle, 6.3%; nominal I P i <= 0.026). Https://doi.org/10.1093/bjd/ljad060 DearEditor, Psoriatic lesions can occur on difficult-to-treat areas such as the face or intertriginous regions.[1] While topical corticosteroids may be effective for treating psoriasis, risk of local skin, ocular and systemic side-effects require cautious use, especially in these locations.[2],[3] Topical vitamin D analogues are less effective than corticosteroids and may be associated with local side-effects and should not be applied to facial skin.[[2], [4]] Thus, patients with psoriasis need a topical treatment that is effective and can be used safely on a wide range of anatomical areas without restrictions on treatment duration or site of application. [Extracted from the article]

The Psoriasis Area and Severity Index (PASI) is the most widely used clinical measure in clinical trials to assess disease severity of plaque psoriasis. However, the PASI is not a precise measure of severity with less precision when the regional area of involvement is < 10% of the BSA of a specific anatomical region. Degradation of precision results from the area score defaulting to '1' when the area of involvement within an anatomical region falls between 0% and 10% of the BSA for a given anatomical region. We describe a modification to the PASI, termed PASI-high discrimination (PASI-HD), for determination of more accurate psoriasis severity in body regions where < 10% of the body surface area is affected. The methodology for assessing disease severity in these conditions is described. [ABSTRACT FROM AUTHOR]

Itch is a major complaint among patients with seborrheic dermatitis (SD). Roflumilast is a selective, nonsteroidal, highly potent phosphodiesterase-4 inhibitor under investigation as a once-daily foam for treatment of SD. This phase 3 randomized, parallel-group, double-blind, vehicle-controlled trial (NCT04973228) was conducted in patients ≥9 years old with at least moderate SD affecting scalp and/or nonscalp areas. Patients were randomized 2 : 1 to apply once-daily roflumilast foam 0.3% (n = 304) or vehicle (n = 153) for 8 weeks. The primary efficacy endpoint was Investigator Global Assessment (IGA) success (IGA of Clear or Almost Clear plus ≥2-grade improvement from baseline) at Week 8. Secondary efficacy endpoints included Worst Itch Numeric Rating Scale (WI-NRS), which was completed daily by patients. Safety and local tolerability were also evaluated. Overall, significantly more roflumilast-treated patients than vehicle-treated patients achieved IGA success (79.5% vs. 58.0%; P < 0.0001) and IGA status of Clear (50.6% vs. 27.7%; P < 0.0001) at Week 8. Significantly greater percentages of roflumilast- than vehicle-treated patients had ≥4-point improvement on WI-NRS at Weeks 2 (32.7% vs. 15.5%; P = 0.0016), 4 (47.6% vs. 29.1%; P = 0.0007) and 8 (62.8% vs. 40.6%; P = 0.0001). Greater improvement in itch was observed among roflumilast-treated patients as early as 48 h after the first application (mean percent change from baseline: −27.87% vs. −13.11%; nominal P = 0.0024). Local tolerability and safety were favorable. Once-daily roflumilast foam provided improvement across multiple efficacy endpoints including rapid itch improvement, while demonstrating favorable safety and tolerability. [ABSTRACT FROM AUTHOR]

Previous examination in a small number of individuals with Williams syndrome (also referred to as Williams-Beuren syndrome) has shown subtly softer skin and reduced deposition of elastin, an elastic matrix protein important in tissue recoil. No quantitative information about skin elasticity in individuals with Williams syndrome is available; nor has there been a complete report of dermatologic findings in this population. To fill this knowledge gap, 94 patients with Williams syndrome aged 7-50 years were recruited as part of the skin and vascular elasticity (WS-SAVE) study. They underwent either a clinical dermatologic assessment by trained dermatologists (2010 WSA family meeting) or measurement of biomechanical properties of the skin with the DermaLab™ suction cup (2012 WSA family meeting). Clinical assessment confirmed that soft skin is common in this population (83%), as is premature graying of the hair (80% of those 20 years or older), while wrinkles (92%), and abnormal scarring (33%) were detected in larger than expected proportions. Biomechanical studies detected statistically significant differences in dP (the pressure required to lift the skin), dT (the time required to raise the skin through a prescribed gradient), VE (viscoelasticity), and E (Young's modulus) relative to matched controls. The RT (retraction time) also trended longer but was not significant. The biomechanical differences noted in these patients did not correlate with the presence of vascular defects also attributable to elastin insufficiency (vascular stiffness, hypertension, and arterial stenosis) suggesting the presence of tissue specific modifiers that modulate the impact of elastin insufficiency in each tissue. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The objective of the study was to determine the prevalence of pediatric human immunodeficiency virus 1 ( HIV-1) mucocutaneous manifestations in the era of highly active antiretroviral therapy ( HAART). We conducted population-based, prospective, multicenter pediatric HIV-1 surveillance in 276 children with perinatally acquired HIV-1 from 1988 to 2009. Centers for Disease Control and Prevention ( CDC)-defined HIV-1 related mucocutaneous conditions among the 276 children were: category A ( n = 152), B ( n = 60), and C ( n = 1). Nearly half of the category A and B diagnoses (43.4% [66/152] and 35.0% [21/60], respectively) occurred in the first year of life, with 59.2% (90/152) and 61.7% (37/60), respectively, occurring in the first 2 years of life. The most frequent infectious diagnosis was oropharyngeal thrush ( n = 117, 42.4%); the most common inflammatory diagnosis was diaper dermatitis ( n = 71, 25.7%). There was a temporal decline in the prevalence of A (pre- HAART cohort, 123; post- HAART cohort, 29; p < 0.01) and B (pre- HAART, 55; post- HAART, 5; p < 0.01) mucocutaneous diagnoses. In children with perinatal HIV-1, there was a significant decline in CDC category A and B mucocutaneous diagnoses by temporal cohort, consistent with the introduction of antiretroviral medications and HAART. Clinical category A and B mucocutaneous diagnoses were most common in the first 2 years of life, emphasizing the importance of early HIV-1 testing and HAART initiation. [ABSTRACT FROM AUTHOR]

The natural history of inherited epidermolysis bullosa ( EB) varies significantly across subtypes. When confronted with an infant suspected to have EB, rapidly determining the type and subtype is critical in counselling families accurately about the infant's diagnosis and prognosis. Although transmission electron microscopy ( TEM) has been considered the criterion standard for EB diagnosis, immunofluorescence microscopy ( IFM) using monoclonal antibodies ( mAbs) to EB-specific basement membrane zone proteins has several advantages, but few studies have evaluated the diagnostic utility of IFM. We sought to evaluate the clinical utility of IFM using an expanded panel of EB-specific mAbs. This was a retrospective review of pathology reports from infants younger < 1 year old with suspected EB primarily analyzed with IFM by the Stanford Dermatopathology service. Seventy-seven cases were identified for analysis, of which 20 were suboptimal for IFM analysis. Fifty-five cases were diagnosed with EB and classified as follows: EB simplex ( n = 5), junctional EB ( n = 31), dystrophic EB ( n = 19). TEM was available in 36 of 55 cases (65%). IFM with an expanded panel of EB-specific mAbs should be considered the first-line diagnostic test to evaluate infants with clinically suspected EB. [ABSTRACT FROM AUTHOR]

Warts are common and are a challenge to treat in some children, especially immunocompromised children and those who fail or cannot tolerate salicylic acid preparations and cryotherapy. Cidofovir, a nucleotide analogue with antiviral activity, has demonstrated promising results when compounded into a topical form to treat refractory warts. We present a retrospective institutional review of 12 children with refractory verrucae treated with 1% to 3% topical cidofovir compounded in an unscented moisturizing cream, applied every other day to daily. In our institutional series, only three patients (25%) demonstrated complete clearance of their verrucae. An additional four patients (33%) demonstrated partial clearance. Our experience using topical cidofovir has been less successful than previous institutional reviews, possibly because we used a lower concentration and less-frequent dosing. More studies are needed to better characterize the efficacy, safety, and dosing of topical cidofovir for the treatment of refractory warts. [ABSTRACT FROM AUTHOR]

Acro-dermato-ungual-lacrimal-tooth (ADULT) syndrome is a rare, autosomal dominant form of ectodermal dysplasia due to TP63 mutations. ADULT syndrome is much less common than the more classical forms of TP63-associated ectodermal dysplasias, such as ectrodactyly-ectodermal dysplasia-cleft lip/palate (EEC) syndrome and ankyloblepharon-ectodermal defects-cleft lip/palate syndrome. ADULT syndrome is characterized by ectrodactyly, syndactyly, and excessive freckling, in addition to more typical ectodermal defects, including hypodontia, lacrimal duct anomalies, hypotrichosis, and onychodysplasia. Unlike some of the other TP63-associated ectodermal dysplasias, ADULT syndrome lacks clefting and ankyloblepharon. Here, we report a three-generation family with ADULT syndrome due to an R243W mutation in TP63, a mutation that has previously been described in one patient with ADULT syndrome and eight unrelated patients with EEC syndrome. [ABSTRACT FROM AUTHOR]

Terra firma-forme dermatosis is an idiopathic condition characterized by acquired, dirtlike plaques despite normal hygiene. A diagnosis can be reached by removing lesions with gentle alcohol swabbing. Although Terra firma-forme dermatosis was first described more than 20 years ago and is thought to be not uncommon in clinical practice, it has never been systematically studied. There are few publications about this condition, including no case series of more than six patients. In particular, little is known about the incidence, peak age groups, and most common locations of Terra firma-forme dermatosis. A retrospective review was conducted to identify cases of Terra firma-forme dermatosis in a single-provider practice consisting of 55% pediatric and 45% adult patients. Thirty-one patients with Terra firma-forme dermatosis were identified, including 10 who presented with Terra firma-forme dermatosis as their primary concern. Only two patients were older than 17 years. The median duration of lesions was 4 months. The most common lesion locations were the neck, ankles, and face. Before presenting to the dermatology clinic, three patients had undergone endocrine evaluations, and four had been prescribed topical corticosteroids. Terra firma-forme dermatosis is relatively common and most often occurs in children on the neck or posterior malleolus. This series exemplifies the importance of recognizing Terra firma-forme dermatosis so as to provide rapid relief for patients and avoid unnecessary tests and treatments. [ABSTRACT FROM AUTHOR]

Acute genital ulcers rarely occur in nonsexually active young girls. When present, they can cause significant physical and emotional distress for the patient and her parents, and prompt an evaluation for sexual abuse and sexually transmitted diseases. With this review, we aim to further characterize acute genital ulcers in nonsexually active young girls by reviewing the medical records of patients with this disorder and to offer an approach to the diagnosis, evaluation, and treatment of acute genital ulcers based on our understanding and knowledge of this condition. We retrospectively review our understanding and knowledge of acute genital ulcers in nonsexually active girls at a pediatric hospital. A review of the recent literature on acute genital ulcers and a multidisciplinary approach to the diagnosis, evaluation, and treatment of acute genital ulcers are also presented. Twelve patients presented with acute genital ulcers, 11 of which were hospitalized for evaluation and pain management. Extensive work-up failed to reveal a specific infectious or autoimmune etiology in all but one patient, who was diagnosed with acute mycoplasma pneumonia. Acute genital ulcers in nonsexually active young girls likely represent a form of idiopathic vulvar aphthosis. Evaluation of a first episode of acute genital ulcers with mild prodromal symptoms should be limited. Treatment consists primarily of supportive care and symptom relief. [ABSTRACT FROM AUTHOR]

Subcutaneous fat necrosis of the newborn is a form of panniculitis that most often occurs in full-term infants with predisposing risk factors. Three neonates with hypoxic ischemic encephalopathy were treated with therapeutic hypothermia and developed extensive subcutaneous fat necrosis. All three infants developed extensive subcutaneous fat necrosis, involving the back, scalp, and arms. Mild, asymptomatic hypercalcemia was noted in one infant in the weeks following the subcutaneous fat necrosis. Hypothermia as a risk factor for subcutaneous fat necrosis is reviewed. Clinicians should be aware of subcutaneous fat necrosis as a possible risk factor and complication associated with asphyxiated newborns who may undergo therapeutic hypothermia. Future studies for therapeutic hypothermia should evaluate neonates for the development of subcutaneous fat necrosis. [ABSTRACT FROM AUTHOR]

We describe six patients who developed orange to red-brown scalp discoloration after application of selenium sulfide-containing shampoos. This phenomenon has been described only once previously. In all of the cases, the discoloration resolved shortly after discontinuing the selenium sulfide. Lightly swabbing with isopropyl alcohol facilitated removal of the discoloration. This simple technique serves as a painless diagnostic method, which may prevent unnecessary evaluation with a biopsy. [ABSTRACT FROM AUTHOR]

Yu GP, Nadeau KC, Berk DR, de Saint Basile G, Lambert N, Knapnougel P, Roberts J, Kavanau K, Dunn E, Stiehm ER, Lewis DB, Umetsu DT, Puck JM, Cowan MJ. Genotype, phenotype, and outcomes of nine patients with T-B+NK+ SCID. Pediatr Transplantation 2011: 15: 733-741. © 2011 John Wiley & Sons A/S. Abstract: There are few reports of clinical presentation, genotype, and HCT outcomes for patients with T-B+NK+ SCID. Between 1981 and 2007, eight of 84 patients with SCID who received and/or were followed after HCT at UCSF had the T-B+NK+ phenotype. One additional patient with T-B+NK+ SCID was identified as the sibling of a patient treated at UCSF. Chart reviews were performed. Molecular analyses of IL7R, IL2RG, JAK3, and the genes encoding the CD3 T-cell receptor components δ (CD3D), ε (CD3E), and ζ (CD3Z) were carried out. IL7R mutations were documented in four patients and CD3D mutations in two others. Three patients had no defects found. Only two of nine patients had an HLA-matched related HCT donor. Both survived, and neither developed GVHD. Five of seven recipients of haploidentical grafts survived. Although the majority of reported cases of T-B+NK+ SCID are caused by defects in IL7R, CD3 complex defects were also found in this series and should be considered when evaluating patients with T-B+NK+ SCID. Additional genes, mutations in which account for T-B+NK+ SCID, remain to be found. Better approaches to early diagnosis and HCT treatment are needed for patients lacking an HLA-matched related donor. [ABSTRACT FROM AUTHOR]

Accurately measuring the size of infantile hemangiomas is critical for objectively quantifying their growth, involution, and treatment response. Volumetric measurements are particularly appropriate because hemangiomas tend to mark out their territory early on and then grow and involute volumetrically. To our knowledge, only two publications have proposed bedside methods for measuring hemangioma volume. In these two publications, the authors modeled hemangiomas as perfect spheres or half-spheres, but many hemangiomas more closely approximate ellipsoids, with each of their axes in three dimensions having different, rather than equal, lengths. We present an alternative bedside method for calculating hemangioma volume, using a formula derived with calculus requiring only three bedside measurements using a disposable paper tape measure. [ABSTRACT FROM AUTHOR]

Cellular phone dermatitis, also known as mobile phone dermatitis, is a recently recognized condition due to either nickel or chromate allergy. Cellular phone dermatitis has most often been reported in young adults and less commonly in adolescents. We describe five adolescents whose cellular phone dermatitis was caused by nickel allergy. [ABSTRACT FROM AUTHOR]

Objective: To present the common features of periocular tinea to aid physicians in future diagnosis and therapy of this condition, because superficial fungal infections on the face are often misdiagnosed owing to the diverse morphologies that they manifest. This is especially true of dermatophytoses involving the periocular region. Methods: A retrospective review was performed of patients with a diagnosis of periocular tinea who were seen between January 2003 and September 2009 in the pediatric dermatology clinic at St. Louis Children's Hospital. Results: Ten cases of periocular tinea were identified (6 male patients and 4 female patients). Common features included prolonged misdiagnosis (all 10 cases), a normal ophthalmologic examination (all 10 cases), and inappropriate corticosteroid application (7 cases). Loss of the eyelashes occurred in all 10 patients. No cases had evidence of other tinea infections on examination. Only 2 cases had the central clearing classically associated with tinea corporis. Seven patients had a potassium hydroxide preparation and/or culture positive for fungal elements. Lesions improved with topical and oral antifungal treatment in all cases, and patients were able to regrow their eyelashes. Conclusion: Periocular tinea should be considered in the differential diagnosis for periocular inflammation, especially in those patients refractory to therapy for more common conditions. Loss of the eyelashes is characteristic of these fungal infections, similar to the hair loss that occurs in kerions associated with tinea capitis. [ABSTRACT FROM AUTHOR]

Pediatric melanoma is difficult to study because of its rarity, possible biological differences in preadolescents compared with adolescents, and challenges of differentiating true melanoma from atypical spitzoid neoplasms. Indeterminant lesions are sometimes designated as melanocytic tumors of uncertain malignant potential (MelTUMPs). We performed a retrospective, single-institution review of melanomas, MelTUMPs and Spitz nevi with atypical features (SNAFs) in patients at 21 years of age and younger from 1995 to 2008. We identified 13 patients with melanoma, seven with MelTUMPs, and five with SNAFs. The median age for melanoma patients was 17 years, 10 for MelTUMPs, and six for SNAFs. Of the 13 melanoma patients, only four were younger than 15 years, while six were adolescents, and three were young adults. Nine melanoma patients (69%) were female. The most common histologic subtype was superficial spreading. The median depth for melanomas was 1.2 mm, and 3.4 mm for MelTUMPs. Microscopic regional nodal involvement detected on elective or sentinel lymph node (SLN) dissection was present in 2/10 (20%) of primary melanomas and 2/6 (33%) of Mel-TUMPs. Complete lymphadenectomy was performed on four melanoma patients, with three positive cases. Patient outcome through March 31, 2009 revealed no in-transit or visceral metastasis in patients with MelTUMPs or SNAFs. One SLN-positive patient (8%) with melanoma developed recurrent lymph node and liver metastasis and died 15 months after primary diagnosis. Our data highlight the rarity, female predominance, and significant rate of SLN positivity of pediatric melanoma. The high rate of MelTUMPs with regional nodal disease reinforces the need for close follow-up. [ABSTRACT FROM AUTHOR]

Objective: To characterize the clinical changes in clinically distinctive scalp nevi over time in children to help guide management and avoid misdiagnosis as melanoma. Design: Cohort study. Setting: Washington University School of Medicine pediatric dermatology clinics. Patients: Of 93 patients younger than 18 years with photographically documented, clinically distinctive scalp nevi, 28 (30%) consented to participate. Minimum follow-up from the initial visit was 1 year. Collectively, these patients had 44 scalp nevi at the initial visit. No patient had a personal diagnosis of melanoma or dysplastic nevus syndrome. Main Outcome Measures: Clinical changes in scalp nevi as determined using the ABCDE scoring system (ie, asymmetry, border irregularity, color variegation, diameter >6 mm, and evolution/elevation from initial tofollow- up images) on initial and follow-up photographs of scalp nevi. Results: Overall, 77% of the clinically distinctive scalp nevi (34 of 44) showed clinical signs of change during mean follow- up of 2.8 years. Of those with changes, 18 (53%) became more atypical and 16 (47%) became less atypical since the initial examination. None of the changes were concerning for melanoma. The mean total scalp nevus count was 2.6. Scalp nevi represented approximately 6% of totalbody nevi. The number of scalp nevi increased with age. Boys had 1.5 times the number of scalp nevi as girls (P=.03). Conclusions: Scalp nevi are clinically dynamic in childhood. These changes include an increase or a decrease in atypical features and occur in all age groups. This preliminary study does not support excisional biopsies but does support physician evaluation of scalp nevi evolution and serial photography of clinically distinctive lesions. [ABSTRACT FROM AUTHOR]

Objective: To determine the prevalence of aquagenic wrinkling of the palms (AWP) in patients with cystic fibrosis (CF) compared with control patients, and evaluate for genotype-phenotype correlations. Since its first description over 30 years ago, AWP has frequently been anecdotally associated with CF, but this association has not been confirmed in a rigorous prospective casecontrol study. Design: Blinded comparison. Setting: The CF and dermatology clinics at St Louis Children's Hospital. Participants: Forty-four individuals with CF from a CF clinic and 26 controls from a dermatology clinic. Intervention: Participants were tested for AWP using 3 minutes of water immersion with room-temperature tap water. Main Outcome Measure: The degree of AWP was scored from 0 (no wrinkling) to 4 (severe wrinkling) by 3 blinded physicians. For genotype-phenotype correlations, patients with CF were divided into those homozygous for the ΔF508 mutation and those with other genotypes. Results: The mean AWP score of the CF group was significantly higher than the mean score of the control group (1.5 vs 0.6; P<.001). Patients with CF who were homozygous for the ΔF508 mutation (n=27) had significantly higher scores than patients with CF who were not homozygous for the ΔF508 mutation (n=17) (1.7 vs 1.1; P=.02). The 17 patients with CF who were not homozygous for the ΔF508 mutation still had higher scores than the control group (1.1 vs 0.6; P=.03). There was no correlation between sweat chloride concentrations measured at the time of diagnosis and AWP score. Conclusions: Our results confirm the association between AWP and CF. Among patients with CF, greater AWPoccurs in those who are homozygous for the ΔF508 mutation. [ABSTRACT FROM AUTHOR]

The neutrophilic dermatoses are rare disorders, especially in children, and are characterized by neutrophilic infiltrates in the skin and less commonly in extracutaneous tissue. The neutrophilic dermatoses share similar clinical appearances and associated conditions, including inflammatory bowel disease, malignancies, and medications. Overlap forms of disease demonstrating features of multiple neutrophilic dermatoses may be seen. The manuscript attempts to provide an up-to-date review of (i) classical neutrophilic dermatoses, focusing on distinctive features in children and (ii) neutrophilic dermatoses which may largely be pediatric or genodermatosis-associated (Majeed, SAPHO [synovitis, severe acne, sterile palmoplantar pustulosis, hyperostosis, and osteitis] syndrome, PAPA (pyogenic sterile arthritis, pyoderma gangrenosum, and acne), PFAPA (periodic fever with aphthous stomatitis, pharyngitis, and cervical adenopathy), and other periodic fever syndromes, and congenital erosive and vesicular dermatosis healing with reticulated supple scarring). [ABSTRACT FROM AUTHOR]

Background: Acanthosis nigricans is a feature of several syndromes caused by activating mutations of the fibroblast growth factor receptor 3 gene (FGFR3), including Crouzon syndrome with acanthosis nigricans, thanatophoric dysplasia, and severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN syndrome). Observations: We describe a healthy 4-year-old African American girl with generalized acanthosis nigricans since infancy. Her father had a history of acanthosis nigricans since childhood, in addition to Crohn disease, obesity, and adult-onset diabetes mellitus. A pedigree with numerous affected family members was constructed. Other than slightly short stature, no associated anomalies were found, including dysmorphic features or skeletal or neurologic defects. Genetic testing revealed a previously undescribed, heterozygous lysine to threonine mutation at codon 650 of the FGFR3 gene in the 4 affected family members who were tested. Conclusion: Extensive acanthosis nigricans in early childhood, especially with a family history of acanthosis nigricans, may warrant testing for FGFR3 mutations. [ABSTRACT FROM AUTHOR]

Background: Glomuvenous malformations (GVMs) are now considered a separate entity from venous malformations. The rarest type of GVM is the generalized congenital plaque-type GVM. Observations: We present 10 new cases of congenital plaque-type GVM and describe their clinical progression and treatment. Mutations in the glomulin gene were found in those patients who participated in the genetic study. Conclusions: Congenital plaque-type GVMs are unique in their congenital nature, extensive distribution, difficult to diagnose and treat, and progressive involvement after birth. Most cases are familial, yet affected relatives usually have only minor lesions. The lesions of congenital plaque-type GVM are severe, visible at birth, and usually mistaken for extensive venous malformations.Vascular malformations are divided by hemodynamic type into slow-flow and fast-flow lesions. Slow-flow lesions are subcategorized as capillary, lymphatic, and venous.1 Capillary malformations are flat, sharply demarcated, redpink vascular stains of the skin commonly referred to as port-wine stains. These persist throughout life and are characterized histologically by dilated capillaries within the dermis. They slowly increase in size with age. Lymphatic malformations are spongelike collections of abnormal channels and spaces that contain clear lymphatic fluid, causing an excess of fluid to accumulate and dilate the lymphatic channels. This results in swelling of the affected area and, if extensive, can cause enlargement of soft tissues and bones. [ABSTRACT FROM AUTHOR]

Background. The effect of changes in physical exercise on progression of musculoskeletal disability in seniors has rarely been studied. Methods. We studied a prospective cohort annually from 1984 to 2000 using the Health Assessment Questionnaire Disability Index (HAQ-DI). The cohort included 549 participants, 73% men, with average end-of-study age of 74 years. At baseline and at the end of the study, participants were classified as "High" or "Low" vigorous exercisers using a cut-point of 60 min/wk. Pour groups were formed: "Sedentary" (Low→Low; N = 71), "Exercise Increasers" (Low→High; N = 27), "Exercise Decreasers" (High→Low; N = 73), and "Exercisers" (High→High; N = 378). The primary dependent variable was change in HAQ-DI score (scored 0-3) from 1984 to 2000. Multivariate statistical adjustments using analysis of covariance included age, gender, and changes in three risk factors, body mass index, smoking status, and number of comorbid conditions. Participants also prospectively provided reasons for exercise changes. Results. At baseline. Sedentary and Increasers averaged little exercise (16 and 22 exercise min/wk), whereas Exercisers and Decreasers averaged over 10 times more (285 and 212 exercise min/wk; p < .001). All groups had low initial HAQ-DI scores, ranging from 0.03 to 0.08. Increasers and Exercisers achieved the smallest increments in HAQ-DI score (0.17 and 0.11) over 16 years, whereas Decreasers and Sedentary fared more poorly (increments 0.27 and 0.37). Changes in HAQ-DI score for Increasers compared to Sedentary were significantly more favorable (p < .05) even after multivariate statistical adjustment. Conclusions. Inactive participants who increased exercise achieved excellent end-of-study values with increments in disability similar to those participants who were more active throughout. These results suggest a beneficial effect of exercise, even when begun later in life, on postponement of disability. [ABSTRACT FROM AUTHOR]

Objective To review sentinel lymph node (SLN) data from Stanford University Medical Center from January 1, 1997, to January 1, 2004, including rates of SLN positivity according to 2002 American Joint Committee on Cancer (AJCC) tumor classification, relation to other clinical and pathologic prognostic factors, and rates and sites of melanoma recurrence. Design Retrospective case series. Setting Stanford University Medical Center and Stanford melanoma clinics. Patients A total of 274 consecutive patients with primary melanoma who underwent SLN biopsy (SLNB) between January 1, 1997, and January 1, 2004, or who were referred to the Stanford melanoma clinics after SLNB and were followed up through March 2005. Interventions All patients underwent standard wide local excision of their primary tumors and SLNB with intradermal injection of isosulfan blue dye and/or technetium sulfur colloid. Main Outcome Measure Rates of SLN positivity per 2002 AJCC tumor classification, relation to other clinical and pathologic prognostic factors, and rates and sites of melanoma recurrence in node-negative and node-positive patients. Results Positive SLNs were detected in 39 (15%) of 260 cases, including 0 (0%) of 45 for cutaneous melanomas 1.0 mm thick or less (T1), 21 (18%) of 115 for melanomas 1.01 to 2.0 mm thick (T2), 12 (19%) of 64 for melanomas 2.01 to 4.0 mm thick (T3), and 5 (16%) of 32 for melanomas thicker than 4.0 mm (T4). Median Breslow depths were 1.89 mm for SLN-positive biopsy specimens and 1.50 mm for SLN-negative biopsy specimens (P = .07). The recurrence rate was 46% among SLN-positive patients, with a median time to recurrence of 8 months. Bivariate analysis revealed SLN positivity to be associated with AJCC tumor classification (P = .02), location on the trunk (P = .03), and presence of ulceration (P = .03). By multivariate logistic regression, ulceration (P = .01) was predictive of SLN positivity, whereas SLN status (P< .001), ulceration (P = .02), and location (P = .03) were predictive of recurrent disease. Conclusion Data from the past 8 years confirm the accuracy and prognostic value of SLNB in cutaneous melanoma and the low rate of regional nodal recurrence for SLN-negative patients. [ABSTRACT FROM AUTHOR]

Context The effect of early antiretroviral therapy (ART) on the early progression of perinatal human immunodeficiency virus (HIV) infection is not well defined. Objective To examine early disease progression and survival in a population-based cohort with perinatal HIV infection in relation to year of birth and use of ART. Design, Setting, and Patients Retrospective study of temporal trends in early progression of perinatal HIV infection among 205 HIV-infected children in Northern California born between January 1, 1988, and December 31, 2001, and followed up through age 3 years. Main Outcome Measures Prevalence of and age at progression to a first US Centers for Disease Control and Prevention category C diagnosis relative to year of birth, type of ART, and age at initiation of therapy. Results Of 205 children, 134 (65%) received ART and/or Pneumocystis jiroveci pneumonia prophylaxis. By age 3 years, 81 (40%) progressed to a category C diagnosis, 41 (51%) of whom died. Untreated children were significantly more likely to progress to a category C diagnosis (62% [44/71] untreated vs 28% [37/134] treated children, P<.001); none of 23 infants who received triple ART progressed to category C. However, even without triple ART, very early mono/dual ART (by age 2 months vs 3-4 months) was associated with delayed and decreased progression to category C (P = .02). Of 33 children born between January 1, 1996, and December 31, 2001, only 7 (21%) progressed to category C (P = .02 compared with 1988-1995), 6 of 7 of whom received no therapy. More recent year of birth and more advanced therapy were associated with improved survival. Conclusions This population-based cohort demonstrated decreased early HIV progression and improved survival at age 3 years, associated with more advanced therapy. Although limited by small sample size, the findings suggest that very early treatment, even without triple ART, was associated with improved outcome. [ABSTRACT FROM AUTHOR]

Some fruit juices have very high potassium content. However, only several cases of juice-induced hyperkalemia have been reported that involved non-psychiatric, diabetic outpatients with renal compromise. We present a highly unusual case of a 66-year-old non-diabetic, schizophrenic woman with psychogenic polydipsia and normal renal function who developed hyperkalemia secondary to excessive orange juice consumption while an inpatient. In addition to demonstrating this previously undescribed medical comorbidity of schizophrenia, this case highlights the need for careful attention when communicating with both nursing and patients when managing psychogenic polydipsia. [ABSTRACT FROM AUTHOR]

Fordyce spots are benign, enlarged sebaceous glands that commonly present as tiny yellow papules on a variety of body surfaces, including the lips. Although these lesions are asymptomatic, in some patients, they are abundant and conspicuous, leading to concerns regarding their cosmetic appearance. The response of Fordyce spots to isotretinoin therapy is poorly documented in the literature, which contains only one case report of an affected patient treated with a short course of isotretinoin (35 mg/kg in total). Herein, we report dichotomous long-term response to a standard course of isotretinoin in two patients with Fordyce spots of the lips and concomitant acne. [ABSTRACT FROM AUTHOR]

Primary hyperhidrosis is a common disorder affecting children and adolescents, and it can have a significant negative psychosocial effect. Treatment for pediatric hyperhidrosis tends to be limited by low efficacy, low adherence, and poor tolerance. Oral glycopyrrolate is emerging as a potential second-line treatment option, but experience with safety, efficacy, and dosing is especially limited in children. We present an institutional review of 12 children with severe, refractory hyperhidrosis treated with oral glycopyrrolate; 11 (92%) noted improvement and 9 (75%) would recommend oral glycopyrrolate to their friends. No significant side effects were noted. Our retrospective analysis suggests that oral glycopyrrolate is safe and effective in children with hyperhidrosis. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 14-year-old Causcasian girl presented with trichodysplasia spinulosa (TS) three years after lung transplantation. Physical examination showed several papules with follicular keratoses mostly in the central face. Several drugs were administered to the patient including methotrexate, prednisone, and tobramycin.

Several types of vascular anomalies have been described in patients with Turner syndrome, including cutaneous lymphatic malformations, vascular anomalies of the heart and aorta, acral venous malformations, and intestinal vascular anomalies. Angiokeratomas have rarely been reported in patients with Turner syndrome. Here, we describe a 14-year-old girl with Turner syndrome who presented with a 2-year history of tender bluish-black keratotic acral papules. Biopsy showed acral skin with focal epidermal acanthosis that was centered on a dilated superficial vessel, consistent with an angiokeratoma. Lysosomal enzyme assays were normal, and she did not demonstrate any other features of a lysosomal storage disorder. [ABSTRACT FROM AUTHOR]

Multiple Spitz nevi are rare and may occur in agminated, widespread, or dermatomal distributions. Agminated Spitz nevi usually arise in children, presenting on grossly normal, hyperpigmented, or most rarely, hypopigmented skin. We present a child with Langerhans cell histiocytosis who developed bilateral agminated Spitz nevi in the inguinal area. Unusual features included the multifocal distribution, bilateral inguinal location, and co-occurrence with Langerhans cell histiocytosis. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented concerning a case of atypical fibroxanthomas without xeroderma pigmentosum in an 11-year-old boy.

Localized persistent pulmonary interstitial emphysema has rarely been reported in preterm infants in the absence of utilization of mechanical ventilation or continuous positive airway pressure. The relative rarity of this condition might preclude rendering of the correct diagnosis, making patients susceptible to unnecessary surgery and increased morbidity and mortality associated with such intervention. We present a preterm infant who developed respiratory distress and radiographic findings of pulmonary interstitial emphysema on the first day after birth, prior to receiving continuous positive airway pressure or mechanical ventilation. It is important for radiologists to consider localized persistent pulmonary interstitial emphysema in the differential diagnosis of cystic lung lesions in preterm infants, even in the absence of mechanical ventilation. In cases where there is uncertainty, CT imaging can be useful in making the correct diagnosis. [ABSTRACT FROM AUTHOR]

This article presents the case report of a 10-year-old boy diagnosed with gastroenteritis. He reported feeling hungry and on physical examination, was afebrile, in no distress, with intermittent, poorly localizable, non-reproducible tenderness to deep palpation. Microscopic examination revealed early or subacute inflammation. One month postoperatively, he had not experienced recurrent pain. Ten percent of patients with appendicitis report a history of acute of right lower quadrant pain, while 1% have had symptoms for 3 weeks.