Updates on Topical Dyad and Triple Combination Therapies Approved for Acne Vulgaris.

Acne vulgaris is a multifaceted disease characterized by inflammatory and noninflammatory lesions. Topical combination therapies offer a multifaceted approach to acne treatment, with synergistic effects and a broad spectrum of action against multiple factors in acne pathogenesis in one single formulation. Clindamycin phosphate/benzoyl peroxide/adapalene, a combination therapy consisting of clindamycin phosphate 1.2%, benzoyl peroxide (BPO) 3.1%, and adapalene 0.15%, is a novel treatment, the only FDA-approved triple combination drug that offers effective treatment of acne vulgaris. This review aims to provide information on clindamycin phosphate/benzoyl peroxide/adapalene and review the literature on combination topical acne medications approved in the United States. This search was conducted on topical combination therapies for acne, their efficacy, adverse effects, and impacts on quality of life with a specific focus on the newly approved clindamycin phosphate/benzoyl peroxide/adapalene and its sub-component dyads, along with other combinations. PubMed, SCOPUS, Embase, Cochrane, and Web of Science databases were searched for publications in 2018-2023. Primary sources were given priority, and secondary sources such as other reviews were considered to supplement any missing information. It was found that various topical dyad and triad combinations exist for acne vulgaris, including adapalene/BPO, tazarotene/clindamycin, clindamycin/BPO, adapalene/clindamycin, topical tretinoin/azelaic acid, topical tretinoin/BPO, and clindamycin phosphate/benzoyl peroxide/adapalene. Dyad and triple combinations represent a promising, convenient solution for acne management, potentially improving patient adherence due to its single formulation. Clindamycin phosphate/benzoyl peroxide/adapalene exhibited significantly high efficacy in treating both inflammatory and noninflammatory lesions, a minimal side effect profile, although no significant changes in quality-of-life measures. Further research is indicated to assess its long-term efficacy and impact on other acne metrics such as cost, scarring, psychosocial implications, and impact on diverse patient populations.

Retrospective Analysis of Presymptomatic Treatment In Sturge-Weber Syndrome.

Background: Ninety percent of infants with Sturge-Weber syndrome (SWS) brain involvement have seizure onset before 2 years of age; this is associated with worse neurologic outcome. Presymptomatic treatment before seizure onset may delay seizure onset and improve outcome, as has been shown in other conditions with a high-risk of developing epilepsy such as tuberous sclerosis complex. Electroencephalogram (EEG) may be a biomarker to predict seizure onset. This retrospective clinical data analysis aims to assess impact of presymptomatic treatment in SWS. Methods: This two-centered, IRB-approved, retrospective study analyzed records from patients with SWS brain involvement. Clinical data recorded included demographics, age of seizure onset (if present), brain involvement extent (unilateral versus bilateral), port-wine birthmark (PWB) extent, family history of seizure, presymptomatic treatment if received, neuroscore, and anti-seizure medication. EEG reports prior to seizure onset were analyzed. Results: Ninety-two patients were included (48 females), and 32 received presymptomatic treatment outside of a formal protocol (5 aspirin, 16 aspirin and levetiracetam; 9 aspirin and oxcarbazepine, 2 valproic acid). Presymptomatically-treated patients were more likely to be seizure-free at 2 years (15 of 32; 47% versus 7 of 60; 12%; p<.001). A greater percentage of presymptomatically-treated patients had bilateral brain involvement (38% treated versus 17% untreated; p=.026). Median hemiparesis neuroscore at 2 years was better in presymptomatically-treated patients. In EEG reports prior to seizure onset, the presence of slowing, epileptiform discharges, or EEG-identified seizures was associated with seizure onset by 2 (p=.001). Conclusion: Presymptomatic treatment is a promising approach to children diagnosed with SWS prior to seizure onset. Further study is needed, including prospective drug trials, long-term neuropsychological outcome, and prospective EEG analysis to assess this approach and determine biomarkers for presymptomatic treatment.

Precision Dermatology: A Review of Molecular Biomarkers and Personalized Therapies.

The evolution of personalized medicine in dermatology signifies a transformative shift towards individualized treatments, driven by the integration of biomarkers. These molecular indicators serve beyond diagnostics, offering insights into disease staging, prognosis, and therapeutic monitoring. Specific criteria guide biomarker selection, ensuring attributes like specificity, sensitivity, cost feasibility, stability, rapid detection, and reproducibility. This literature review, based on data from PubMed, SCOPUS, and Web of Science, explores biomarkers in Hidradenitis Suppurativa (HS), Psoriasis, Atopic Dermatitis (AD), Alopecia Areata (AA), Vitiligo, and Chronic Spontaneous Urticaria (CSU). In HS, TNF-α, IL-1ß, and MMPs serve as biomarkers, influencing targeted therapies like adalimumab and anakinra. Psoriasis involves biomarkers such as TNF-α, IL-23, and HLA genes, shaping treatments like IL23 and IL17 inhibitors. AD biomarkers include ECP, IL-4, IL-13, guiding therapies like dupilumab and tralokinumab. For AA, lipocalin-2, cytokines, and genetic polymorphisms inform JAK inhibitors' use. Vitiligo biomarkers range from cytokines to genetic markers like TYR, TYRP1, guiding treatments like JAK inhibitors. CSU biomarkers encompass IgE, cytokines, and autologous serum tests, influencing therapies like omalizumab and cyclosporine. Comparing conditions, common proinflammatory markers reveal limited specificity. While some biomarkers aid diagnosis and standard treatments, others hold more scientific than clinical value. Precision medicine, driven by biomarkers, has shown success in skin malignancies. Future directions involve AI-powered algorithms, nanotechnology, and multi-omics integration for personalized dermatological care.

Chest wall bruising from 5-point car seat harness as a mimicker of child abuse.

Bruising rarely presents in infants younger than 9 months who are not ambulatory and is more prevalent among children beginning to walk, or "cruisers." We present the case of a healthy 3-month-old infant with asymptomatic, symmetric, bilateral, large bruises on the bony chest sparing the mid-chest/sternum with a negative non-accidental trauma work-up. The noted pattern of bruises matched the bilateral shoulder straps of a 5-point harness of the car seat belt designed for infants. Awareness of this unique pattern of bruises will help elicit a better-informed history to guide care in an appropriate setting.

Evaluating the clinical efficacy of pulsed dye laser with sirolimus for treatment of capillary malformations: A systematic review.

Port-wine stains (PWS) are capillary vascular anomalies that are often treated with pulsed-dye laser (PDL). Revascularization limits persistent clearance; however, the anti-angiogenic effects of sirolimus (SIRO) may inhibit revascularization. This review aims to determine differences in PWS outcomes when treated with PDL monotherapy or in combination with SIRO. A systematic review was conducted using PubMed, Cochrane, and Embase databases. The following search terms were used: 'port wine stain PDL SIRO', 'port wine stain PDL', and 'port wine stain PDL and topical treatment' with (MeSH) and (Title/Abstract) limits. The search was limited to the English language and human-subject studies conducted between 1 January 2000 and 1 June 2023. Inclusion criteria included studies evaluating SIRO as an adjunct to PDL in patients with PWS. Data extraction and quality assessment were performed by two independent reviewers. A total of nine studies met the inclusion criteria, which included randomized controlled trials (3), case series (2), case reports (3), and a prospective intrapatient study (1), which represented a total of 58 patients. Five studies showed improvement of a measured post-treatment PDL parameter including shortening treatment time and less frequent dosing. A subset of studies (4/9) which did not demonstrate significant clinical improvements exhibited significant photographic evidence of improvement. Heterogeneity among the studies highlights the need for further research and standardization. While adjunctive SIRO shows promise, larger studies and comprehensive evaluation methods are required to establish conclusive safety and efficacy guidelines to shape clinical decision-making.

Management of tinea capitis in infants and children in the United States: A national survey of pediatric dermatologists.

This study aimed to evaluate the current management of tinea capitis in the United States, specifically focusing on patients aged 0-2 months, 2 months to 2 years, and 2 years to 18 years. An online survey, distributed through the Pediatric Dermatology Research Alliance and the Society of Pediatric Dermatology, revealed the following preferences: fluconazole for those under 2 months, griseofulvin for those aged 2 months to 2 years, and terbinafine for those aged 2 years and older. There exists inter-provider variation in tinea capitis treatment regimens within the pediatric dermatology community.

Cutaneous tuberculosis in the pediatric population: A review.

Importance: Tuberculosis (TB) is a significant health concern, affecting over 1.5 million people annually worldwide, with the incidence increasing in the United States from 2020 to 2021. The pediatric population is particularly vulnerable to TB. Extrapulmonary manifestations of TB include cutaneous tuberculosis (CTB). Observations: There are 8 forms of CTB. Lupus vulgaris (LV) is the second most common form of pediatric CTB which presents nontender plaques or nodules with ulceration that progress to well-defined, scaly plaques. Tuberculous chancre results from exogenous inoculation and lesions contain large amounts of acid-fast bacilli (AFB). Clinically, tuberculous chancre presents as erythematous papules which form firm nontender ulcers. Tuberculosis verrucose cutis (TVC) presents as small papules surrounded by inflammation that develops into a wart-like lesion. Periorificial lesions are rare and present as painful ulcers in the oral or perineal regions. Scrofuloderma is the most common form of pediatric CTB and presents as nodules that ulcerate, forming purulent sinus tracts. Tuberculosis miliaris cutis disseminate presents as widespread papules and crusted vesicles. Metastatic abscesses present as multiple nodules that may ulcerate or form draining sinus tracts. Lastly, tuberculid forms include lichen scrofulosorum (LS), which presents as lichenoid papules which may form plaques and scale, and papulonecrotic tuberculid, which presents as necrotic papules. All forms of cutaneous tuberculosis can be treated with the standard 6-month, four-drug anti-tuberculosis treatment (ATT). Some cases of CTB may require debriding and surgical management in addition to ATT. Conclusions and Relevance: Determining the type of CTB can be challenging clinically. Histopathology is needed to make the diagnosis. Chest x-ray and a review of systems should be obtained for CTB patients to determine if there are other extrapulmonary manifestations of TB. All types are treated with 6 months of ATT.

Multiple General Anesthesia in Children: A Systematic Review of Its Effect on Neurodevelopment.

The effect of multiple general anesthesia (mGA) procedures administered in early life is a critical theme and has led the Food and Drug Administration (FDA) to issue an alert. This systematic review seeks to explore the potential effects on neurodevelopment of mGA on patients under 4 years. The Medline, Embase and Web of Science databases were searched for publications up to 31 March 2021. The databases were searched for publications regarding "children multiple general anesthesia OR pediatric multiple general anesthesia". Case reports, animal studies and expert opinions were excluded. Systematic reviews were not included, but they were screened to identify any possible additional information. A total of 3156 studies were identified. After removing the duplicates, screening the remaining records and analyzing the systematic reviews' bibliography, 10 studies were considered suitable for inclusion. Comprehensively, a total cohort of 264.759 unexposed children and 11.027 exposed children were assessed for neurodevelopmental outcomes. Only one paper did not find any statistically significant difference between exposed and unexposed children in terms of neurodevelopmental alterations. Controlled studies on mGA administered before 4 years of age support that there might be a greater risk of neurodevelopmental delay in children receiving mGA, warranting the need for careful risk/benefit considerations.

Genetic testing in the evaluation of individuals with clinical diagnosis of atypical Sturge-Weber syndrome.

Sturge-Weber Syndrome (SWS) is a rare vascular malformation disorder characterized by abnormal blood vessels in the brain, skin, and eye. SWS is most commonly caused by a somatic mosaic GNAQ-p.Arg183Gln variant. In this series, 12 patients presented for clinical evaluation of SWS but were noted to have atypical features, and therefore germline and/or somatic genetic testing was performed. Atypical features included extensive capillary malformation on the body as well as the face, frontal bossing, macrocephaly, telangiectasia, overgrowth of extremities, absence of neurologic signs and symptoms, and family history of vascular malformations. Five patients had a somatic GNAQ or GNA11 pathogenic variant, one patient had a somatic mosaic likely-pathogenic variant in PIK3CA, and another one had a somatic mosaic deletion that disrupted PTPRD. The other five patients had germline variants in RASA1, EPHB4, or KIT. Our findings suggest that patients presenting for SWS evaluation who have atypical clinical characteristics may have pathogenic germline or somatic variants in genes other than GNAQ or GNA11. Broad germline and somatic genetic testing in these patients with atypical findings may have implications for medical care, prognosis, and trial eligibility.

Mucocutaneous manifestations of congenital syphilis in the neonate: A review of a surging disease.

Syphilis is an infection caused by Treponema pallidum. It is most commonly acquired through sexual transmission, although it can also be transmitted vertically across the placenta, resulting in congenital syphilis. Even with improved public health measures, testing, and treatment capabilities, primary, secondary, and congenital syphilis have all surged since 2012. Given this marked increase in both incidence and prevalence, here we present a comprehensive review of the clinical presentation, treatment, and management of congenital syphilis, with particular consideration given to the mucocutaneous manifestations of the disease in neonates.

Disruption of the HIF-1 pathway in individuals with Ollier disease and Maffucci syndrome.

Ollier disease (OD) and Maffucci Syndrome (MS) are rare disorders characterized by multiple enchondromas, commonly causing bone deformities, limb length discrepancies, and pathological fractures. MS is distinguished from OD by the development of vascular anomalies. Both disorders are cancer predisposition syndromes with malignancies developing in ~50% of the individuals with OD or MS. Somatic gain-of-function variants in IDH1 and IDH2 have been described in the enchondromas, vascular anomalies and chondrosarcomas of approximately 80% of the individuals with OD and MS. To date, however, no investigation of germline causative variants for these diseases has been comprehensively performed. To search for germline causative variants, we performed whole exome sequencing or whole genome sequencing of blood or saliva DNA in 94 unrelated probands (68 trios). We found that 7 had rare germline missense variants in HIF1A, 6 had rare germline missense variants in VHL, and 3 had IDH1 variants including 2 with mosaic IDH1-p.Arg132His variant. A burden analysis using 94 probands assigned as cases and 2,054 unrelated individuals presenting no OD- or MS-related features as controls, found that variants in HIF1A, VHL, and IDH1 were all significantly enriched in cases compared to controls. To further investigate the role of HIF-1 pathway in the pathogenesis of OD and MS, we performed RNA sequencing of fibroblasts from 4 probands with OD or MS at normoxia and at hypoxia. When cultured in hypoxic conditions, both proband and control cells showed altered expression of a subset of HIF-1 regulated genes. However, the set of differentially expressed genes in proband fibroblasts included a significantly reduced number of HIF-1 regulated genes compared to controls. Our findings suggest that germline or early post-zygotic variants identified in HIF1A, VHL, and IDH1 in probands with OD and MS underlie the development of the phenotypic abnormalities in a subset of individuals with OD and MS, but extensive functional studies are needed to further confirm it.

Heterogeneous cutaneous findings associated with intrauterine HSV infection: A case series and literature review.

BACKGROUND/OBJECTIVE: Herpes simplex virus (HSV) infection acquired in utero may present with non-vesicular dermatologic findings in affected newborns, which may pose a diagnostic dilemma. We aimed to describe and assess the range of non-vesiculobullous skin lesions that neonates with intrauterine HSV infection may manifest at birth. METHODS: We collected a multicenter case series and conducted a literature review of neonates with intrauterine HSV infection presenting with non-vesiculobullous cutaneous lesions. RESULTS: Twenty-two cases were reviewed, including six managed clinically by members of our team and 16 identified in the literature. Four (18%) were associated with twin pregnancies, and thirteen (59%) cases occurred in premature infants. Only four (18%) mothers had a documented history of HSV infection. Twelve (55%) cases resulted in poor outcomes, including long-term neurologic sequelae or death. Cutaneous manifestations included erosions, ulcerations, crusted papules or plaques, calcinosis cutis, excoriations, macules (erythematous, hypopigmented, or hyperpigmented), cutaneous atrophy, contractures, and bruising. About one-third of neonates developed new-onset vesicular lesions within a week of birth; in each of these cases, accurate diagnosis and therapy were delayed until appearance of vesicles. CONCLUSIONS: The range of dermatologic findings associated with intrauterine HSV is extremely broad, and the various morphologies present at birth likely reflect different stages of the ongoing evolution of an HSV infection that began in utero. Clinicians should have a low threshold for HSV testing in premature neonates born with atypical cutaneous lesions, since early detection and treatment of HSV may reduce morbidity and mortality from systemic complications.

Tinea capitis: advances and a needed paradigm shift.

PURPOSE OF REVIEW: Tinea capitis, a superficial infection of the scalp, is the most common pediatric dermatophyte fungal infection worldwide and is particularly common in the USA in low-income, low-resource settings. There are still gaps in knowledge and heterogeneities in practice in terms of diagnostic and management strategies. Furthermore, there are no clinical guidelines for management and treatment of tinea capitis in the USA. This review aims to summarize recent advances, recommend optimal management for the practicing pediatrician, and identify areas for future research for tinea capitis. RECENT FINDINGS: Trichophyton tonsurans infections are best treated with terbinafine and Microsporum canis infections are best treated with griseofulvin. Trichophyton tonsurans is the predominant cause of tinea capitis in the USA, although the main gold standard of treatment in the USA is griseofulvin. Dermatophyte antifungal resistance is an active area of investigation but seems to not be of current concern for tinea capitis in the USA. SUMMARY: We recommend all clinical providers ascertain the causative organism in fungal infection, either through fungal culture or newer methods which may become more readily available and cost-effective in the future, such as polymerase chain reaction assay. We also recommend terbinafine as first-line treatment of tinea capitis, with adjustment as necessary after species identification.

A Retrospective Study of Tinea Capitis Management in General Pediatric Clinics and Pediatric Emergency Departments at 2 US Centers.

We examine management practices of tinea capitis at 2 US academic centers. The majority of providers treated tinea capitis with the oral antifungal agent griseofulvin and did not obtain a fungal culture. We recommend newer antifungal treatments such as terbinafine and fluconazole and obtaining a fungal culture for effective treatment.

Anesthetic techniques used for pulsed dye laser (PDL) in the treatment of port-wine birthmarks: An exploratory assessment of current attitudes and practice patterns among pediatric dermatologists in the United States.

BACKGROUND/OBJECTIVES: Pulsed dye laser (PDL) is the gold standard for treating port-wine birthmarks (PWBs), but no consensus exists regarding anesthetic techniques when performing PDL for PWB. Given potential adverse neurocognitive effects from general anesthesia (GA) exposure in early childhood, we sought to establish current attitudes and practice patterns regarding anesthesia when treating PWB with PDL. METHODS: An electronic REDCap survey was distributed to members of the Pediatric Dermatology Research Alliance (PeDRA) and the Society for Pediatric Dermatology (SPD) via email. Aggregate, anonymized results were reported. RESULTS: Among 47 respondents, the majority (83%) identified as board-certified pediatric dermatologists. When treating children <4 years old, 70% endorsed some use of topical anesthesia. Although 87% reported concerns about long-term side effects on development and school performance affecting their pursuit of GA, 61% reported use of GA for PDL in children <4 years old. All 4 (100%) respondents whose PDL was located in the operating room (OR) setting reported use of GA, compared to 6 of 17 (35%) respondents whose PDL machine was not located in the OR. Providers were more likely to use GA in patients between 1 and 4 years old (70%) compared to those <1 year old (2%). CONCLUSIONS: Diverse practice patterns reiterate the need for a standardized anesthetic approach for PDL in young children and continued research on other factors (ie, location/accessibility of PDL, lesion size) impacting anesthesia choices. Given potential neurodevelopmental risks associated with GA, specific guidance to effectively minimize its use in favor of topical anesthetics should be provided.

Sirolimus Treatment in Sturge-Weber Syndrome.

BACKGROUND: Sturge-Weber syndrome is a rare neurovascular disorder associated with capillary malformation, seizures, cognitive impairments, and stroke-like episodes (SLEs), arising from a somatic activating mutation in GNAQ. Studies suggest this mutation may cause hyperactivation of the mammalian target of rapamycin pathway. Sirolimus is an mammalian target of rapamycin inhibitor studied in other vascular anomalies and a potentially promising therapy in Sturge-Weber syndrome. METHODS: Ten patients with Sturge-Weber syndrome brain involvement and cognitive impairments were enrolled. Oral sirolimus was taken for six months (maximum dose: 2 mg/day, target trough level: 4-6 ng/mL). Neuropsychological testing, electroencephalography, and port-wine score were performed at baseline and after six months on sirolimus. Neuroquality of life, adverse events, and Sturge-Weber Syndrome Neurological Score (neuroscore) were recorded at each visit. RESULTS: Sirolimus was generally well tolerated; one subject withdrew early. Adverse events considered related to sirolimus were mostly (15/16) grade 1. A significant increase in processing speed was seen in the overall group (P = 0.031); five of nine patients with available data demonstrated statistically rare improvement in processing speed. Improvements were seen in the neuroquality of life subscales measuring anger (P = 0.011), cognitive function (P = 0.015), and depression (P = 0.046). Three subjects experiencing SLEs before and during the study reported shortened recovery times while on sirolimus. CONCLUSIONS: Sirolimus was well tolerated in individuals with Sturge-Weber syndrome and may be beneficial for cognitive impairments, especially in patients with impaired processing speed or a history of SLE. A future, randomized, placebo-controlled trial of sirolimus in patients with Sturge-Weber syndrome is needed to further understand these potentially beneficial effects.

Psoriasis and mortality in the United States: Data from the National Health and Nutrition Examination Survey.

BACKGROUND: Psoriasis is a multifactorial disease that has been associated with multiple systemic disorders. Despite its role in mediating cardiovascular, metabolic, and pulmonary disorders, few studies have examined the independent mortality risk associated with psoriasis. OBJECTIVE: To determine the independent relationship between psoriasis and all-cause mortality in a nationally representative sample of the US population. METHODS: Retrospective population-based cohort study of adults and adolescents older than 10 years (N = 13 031) who participated in National Health and Nutrition Examination Surveys (2003-2006 and 2009-2010). Psoriasis status was determined from a self-reported medical history questionnaire. Mortality data are linked from national databases. RESULTS: Psoriasis was present in 2.7% of the study population. Over an average median follow-up of 52.3 months, psoriasis was significantly associated with increased mortality risk (HR, 1.99; 95% CI, 1.01-3.93; P = .047) with adjustment for demographics, smoking, and comorbidities including cardiovascular disease, diabetes, chronic obstructive pulmonary disease, cancer, chronic kidney disease, and stroke. These comorbidities mediated 15.5%, 5.9%, 8.7%, 11.7%, 4.2%, and 4.7% of the association between psoriasis and mortality, respectively. CONCLUSION: Psoriasis is independently associated with an increased risk of mortality. This relationship is partially mediated by an increased prevalence of the cardiovascular, infectious, and neoplastic disorders seen among patients with psoriasis.

Pulmonary Manifestations of Skin Disorders in Children.

Systemic diseases often manifest with cutaneous findings. Many pediatric conditions with prominent skin findings also have significant pulmonary manifestations. These conditions include both inherited multisystem genetic disorders such as yellow-nail syndrome, neurofibromatosis type 1, tuberous sclerosis complex, hereditary hemorrhagic telangiectasia, Klippel-Trénaunay-Weber syndrome, cutis laxa, Ehlers-Danlos syndrome, dyskeratosis congenita, reactive processes such as mastocytosis, and aquagenic wrinkling of the palms. This overview discusses the pulmonary manifestations of skin disorders.