VINDICATE-P: A Mnemonic for the Many Comorbidities of Atopic Dermatitis.

Patients with atopic dermatitis (AD) are at increased risk of atopic and non-atopic comorbidities. In fact, the Hanifin and Rajka criteria include allergic and infectious comorbidities as a minor criterion. Despite the well-recognized list of comorbidities, the past 15 years greatly expanded the list of recognized comorbidities of AD. This narrative review focuses on comorbidities of AD using a mnemonic, VINDICATE-P: vascular/cardiovascular, infectious, neoplastic and neurologic, degenerative, iatrogenic, congenital, atopic and autoimmune, traumatic, endocrine/metabolic, and psychiatric. The comorbidities of AD vary by age. More research is needed into the mechanisms of comorbidities and optimal screening strategies in AD patients.

International Dermatology Outcome Measures (IDEOM) - Report from the 2022 Annual Meeting.

BACKGROUND: The International Dermatology Outcome Measures (IDEOM) is a non-profit organization dedicated to the advancement of evidence-based, consensus-driven outcome measures in dermatological diseases. Researchers and stakeholders from various backgrounds collaborate to develop these objective benchmark metrics to further advance treatment and management of dermatological conditions. SUMMARY: The 2022 IDEOM Annual Meeting was held on June 17-18, 2022. Leaders and stakeholders from the hidradenitis suppurativa, acne, vitiligo, actinic keratosis, alopecia areata, itch, cutaneous lymphoma, and psoriatic disease workgroups discussed the progress of their respective outcome-measures research. This report summarizes each workgroup's updates from 2022 and their next steps as established during the 2022 IDEOM Annual Meeting. J Drugs Dermatol. 2023;22(12):1153-1159 doi:10.36849/JDD.7615.

Systematic Review of Lichen Planus Pigmentosus in Children.

BACKGROUND: Pediatric lichen planus (LP) is a relatively uncommon condition, with increased presentation in children with darkly pigmented skin. OBJECTIVE: To understand the small subset of children with lichen planus (LP) manifesting as lichen planus pigmentosus (LPP), a form with thin plaques and extensive hyperpigmentation, generally in the absence of signs of inflammation Methods: This article is a systematic review of the English language literature for cases of lichen planus pigmentosus (LPP) in children. RESULTS: Twenty-one cases were identified including 2 that were linear, 3 inverse types, 1 palmoplantar. In larger series, 2–2.8% of children with lichen planus are affected by this sub-variant. One patient had reported associated oral lesions. Oral and topical corticosteroids, topical tacrolimus, and ultraviolet light have been described as successful therapies. CONCLUSIONS: LPP is an uncommon but important variant of lichen planus in children. In the presence of dark hyperpigmentation of the skin, a biopsy can help identify LPP. Clinicians should be aware that LPP can follow four patterns: common, inverse, palmoplantar, and linear.J Drugs Dermatol. 2022;21(7):850-853. doi:10.36849/JDD.6760.

International Dermatology Outcome Measures (IDEOM): Report from the 2021 Annual Meeting.

BACKGROUND: International Dermatology Outcome Measures (IDEOM) is a non-profit organization founded in 2013. It is composed of researchers and stakeholders who work to develop evidenced-based outcome measures to enhance research and treatment recommendations of dermatologic diseases. SUMMARY: The 2021 IDEOM Virtual Annual Meeting occurred from November 19-20, 2021. Contributions were made by leaders and stakeholders from the psoriasis, psoriatic arthritis, pediatric hidradenitis suppurativa, acne, vitiligo, actinic keratosis, alopecia areata, itch, and cutaneous lymphoma workgroups. The psoriasis, psoriatic arthritis, and actinic keratosis workgroups provided an overview of their respective instruments for treatment satisfaction and symptom measurement. The inaugural meetings of the itch, alopecia areata, and cutaneous lymphoma workgroups identified unmet needs of their respective diseases and future goals. The acne, vitiligo, and pediatric hidradenitis suppurativa workgroups discussed concerns of quality of life, instruments for symptom measurement, and screening tools. Additionally, a representative from the US Food and Drug Administration was in attendance and presented an update on topical drugs and generics. This report provides a summary of workgroup updates from the past year and future directions established during the meeting. KEY MESSAGES: This report summarizes progress made by each IDEOM workgroup at the 2021 IDEOM Virtual Annual Meeting. J Drugs Dermatol. 2022;21(8):867-874. doi:10.36849/JDD.6974.

Short and Long-Term Outcomes of 308-nm Laser for Pediatric Vitiligo.

Pediatric vitiligo is often challenging to treat. Children with vitiligo experience stigma, bullying, and emotional distress. The long-term outcome of therapeutics used to treat pediatric vitiligo has been poorly documented in the literature. It is, therefore, hard to counsel patients on the expected long-term results of therapy. We sought to address outcomes in pediatric vitiligo treated with a 308-nm laser. An IRB-exempt chart review was conducted in June of 2016 of children undergoing active 308-nm laser in the first half of 2016. Demographic data, location of disease, therapeutic parameters of the 308-nm laser, and outcomes were recorded at that time. In 2021, the long-term outcomes were analyzed through chart review addressing pigmentation retained at later office visits. Initial repigmentation was noted in 86.7% of the face, 80% of the body, and 61.7% of the extremities. An average of 3.38 years of follow-up was recorded. Scoring extent of vitiligo using 18 site-scoring was helpful in identifying individuals who are less likely to respond to 308-nm laser, but needs broader evaluation. During that time, repigmentation was noted to be retained in 80% of facial, 40% of the body, and 20% of extremity lesions. Pediatric vitiligo responds well to the 308-nm laser, with the best retention of repigmentation for facial lesions. Patients and parents should be counseled on the likelihood of long-term retention of repigmentation and regarding the need for the ongoing management of vitiligo even after repigmentation is initially achieved after 308-nm laser therapy. J Drugs Dermatol. 2022;21(7):773-775. doi:10.36849/JDD.6895.

The genetics and diagnosis of pediatric neurocutaneous disorders: Neurofibromatosis and tuberous sclerosis complex.

Neurofibromatosis (NF) and tuberous sclerosis complex (TSC) are the two most common neurocutaneous disorders, both transmitted as autosomal dominant or, in the case of NF, also as a mosaic condition. The causative genetic mutations in these neurocutaneous disorders can lead to benign skin changes or uninhibited growth and proliferation in multiple organ systems due to the loss of tumor suppression in mitogen-activated protein kinase and mammalian target of rapamycin signaling pathways. Common clinical features in NF include pigmented lesions, known as café au lait patches, neurofibromas, intertriginous freckles (Crowe's sign), and benign fibrous growths, such as hamartomas in multiple organ systems. Common clinical features in TSC include hypopigmented macules, known as ash leaf spots, in addition to neurologic sequelae, such as autism, seizures, and developmental delays. Advances in genetic sequencing technologies have allowed an exponential expansion in the understanding of NF and TSC. Consensus criteria have been established for both diagnoses that can be confirmed in most cases through gene testing. Once diagnosed, the clinical and diagnostic value of disease-specific surveillance include early identification of benign and malignant tumors. Genetic counseling is important for informed reproductive decision-making for patients and at-risk family members. The improvement in understanding of pathways of pathogenic disease development and oncogenesis in both conditions have produced a new series of therapeutic options that can be used to control seizures and tumor growth. Tremendous advances in life expectancy and quality of life are now a reality due to early introduction of seizure control and novel medications. While we lack cures, early institution of interventions, such as seizure control in tuberous sclerosis, appears to be disease-modifying and holds immense promise to offer patients better lives.

Association of atopic dermatitis with delinquent behaviors in US children and adolescents.

Childhood atopic dermatitis (AD) is associated with chronic itch, pain and sleep disturbance, which may predispose children to high-risk behaviors in their school and home environments. We examined the association between AD and delinquent/high-risk behaviors in children and adolescents. Data were analyzed from The Fragile Families and Child Wellbeing Study, a longitudinal birth cohort study consisting of 4898 children born in urban cities between 1998 and 2000. A 1-year history of AD was associated with ≥ 75th percentile of mean delinquent behavior scores at age 9 (adjusted odds ratio (aOR) [95% confidence interval] 1.39 [1.14-1.68]), but not age 15 (1.05 [0.86-1.29]). At age 9, a 1-year history of AD was associated with a higher number of delinquent behaviors (adjusted risk ratio [95% CI] 1.12 [1.03-1.23]). AD at ages 5 (aOR [95%CI] 1.31 [1.04-1.64]) and 9 (1.38 [1.14-1.67]) was associated with the highest quartile of mean delinquent behavior scores at ages 9 or 15. Children with AD persisting at multiple age groups had significantly increased odds of ≥ 75th percentile of mean delinquent behavior scores at age 15 (aOR [95%CI] 1.41 [1.09-1.81]). AD was found to be associated with the following delinquent problems: damaging property (aOR [95%CI] 1.38 [1.08-1.77]), cheating on a test (1.62 [1.17-2.26]), fist fight involvement (1.47 [1.21-1.79]) and school suspension (1.36 [1.08-1.71]). This study suggests that childhood AD may precede the onset of delinquent and high-risk behaviors later in childhood and adolescence.

Review article: Emerging issues in pediatric skin of color, Part 2.

Dermatology for pediatric skin of color is the application of dermatology to the genetically diverse and distinctive segment of the pediatric population that includes children of non-White racial and ethnic groups with increased pigmentation including individuals of Asian, Hispanic/LatinX, African, Native American, Pacific Island descent, indigenous people among others with overlap in particular individuals, and mixtures thereof. The discipline of pediatric skin of color can be challenging with difficulty in diagnosis of common conditions due to underlying pigmentation, variations in common hair styling practices, and differences in demographics of cutaneous disease. Whereas some conditions are more common in children of color, other conditions have nuances in clinical appearance and therapeutics with regard to skin color. This article, the second of the series, focuses on inflammatory skin disease nuances, melanocytic disorders, and hypopigmented mycosis fungoides.

Large inflamed facial cysts in teenagers.

BACKGROUND: Facial cysts can become large (1-5 cm) or giant (>5 cm) on the face. OBJECTIVE: To describe the medical course of large and giant facial cysts in adolescents. METHODS: A case series of 11 patients with large or giant facial cysts seen in an outpatient pediatric dermatology practice. RESULTS: Seven patients underwent incision and drainage with culture of cyst contents growing Cutibacterium acnes in six, while the seventh grew Cutibacterium acnes from a frequently worn hat. All patients were treated with traditional therapeutics for cystic acne including intralesional triamcinolone (n = 9), oral antibiotics (n = 10), and isotretinoin (n = 1). Three patients who did not undergo cyst drainage had persistent symptomatology requiring cyst excision, whereas the seven patients whose cysts were drained (3 on initial management and 4 after recurrence) eventually had complete healing without need for surgery. CONCLUSION: Incision and drainage (I & D) and culture of cyst contents can identify cases of cysts related to Cutibacterium acnes. For some cases of large facial cysts related to Cutibacterium acne, I&D combined with conservative acne management (using standard acne guidelines) can prevent the need for surgical excision in some patients. Prospective studies are needed to determine whether this combination of therapy leads to best outcomes clinically and cosmetically.

Emerging therapies in genodermatoses.

The human genome project yielded a compendium of genetic material that has allowed rapid advancement both in the technique of whole exome sequencing and also in the ability to identify single gene defects. The next generation of genetics has investigated how these genes interact in the development of disease, identifying pathways of illness and end organ tissue abnormal development. From the knowledge of single genes and pathways of genodermatosis development arises the opportunity to produce genetic therapies. This contribution reviews some of the exciting, emerging genetic therapies in genodermatoses.

The Effect of Isotretinoin on Vitiligo and Autoimmune Comorbidity.

Several case reports have noted development of vitiligo as a potential side-effect of isotretinoin. In an IRB approved on-line survey of vitiligo patients we queried 1,301 vitiligo patients, 1115 with generalized vitiligo responding as to whether they had taken isotretinoin to address whether this issue was a common phenomenon amongst vitiligo patients. 3.6% of respondents had taken isotretinoin, 1.4% (n=16) before onset of vitiligo, and 2.2% (n=24) after onset of vitiligo. When compared with age-matched vitiligo peers who had not taken isotretinoin before onset of vitiligo (n=64) , isotretinoin use prior to onset of vitiligo was associated with: decreased disease body surface area (conditional logistic regression: OR of BSA≥50% (95% CI)=0.12 (0.03–0.57), P=0.007); decreased odds of body and face involvement when compared with either body or face alone (OR (95% CI)=0.20 (0.06–0.73), P=0.02); and decreased co-morbid autoimmunity (OR (95% CI)=0.17 (0.04–0.58), P=0.01). The volume of isotretinoin usage in vitiligo patients is additionally suggestive of a link between cystic acne and vitiligo. J Drugs Dermatol. 2020;19(6): doi:10.36849/JDD.2020.4938.

Nickel Allergic Contact Dermatitis: Identification, Treatment, and Prevention.

Nickel is a ubiquitous metal added to jewelry and metallic substances for its hardening properties and because it is inexpensive. Estimates suggest that at least 1.1 million children in the United States are sensitized to nickel. Nickel allergic contact dermatitis (Ni-ACD) is the most common cutaneous delayed-type hypersensitivity reaction worldwide. The incidence among children tested has almost quadrupled over the past 3 decades. The associated morbidities include itch, discomfort, school absence, and reduced quality of life. In adulthood, individuals with Ni-ACD may have severe disabling hand eczema. The increasing rate of Ni-ACD in children has been postulated to result from early and frequent exposure to metals with high amounts of nickel release (eg, as occurs with ear piercing or with products used daily in childhood such as toys, belt buckles, and electronics).To reduce exposure to metal sources with high nickel release by prolonged and direct contact with human skin, Denmark and the European Union legislated a directive several decades ago with the goal of reducing high nickel release and the incidence of Ni-ACD. Since then, there has been a global reduction in incidence of Ni-ACD in population-based studies of adults and studies of children and young adults being tested for allergic contact dermatitis. These data point to nickel exposure as a trigger for elicitation of Ni-ACD and, further, provide evidence that legislation can have a favorable effect on the economic and medical health of a population.This policy statement reviews the epidemiology, history, and appearances of Ni-ACD. Examples of sources of high nickel release are discussed to highlight how difficult it is to avoid this metal in modern daily lives. Treatments are outlined, and avoidance strategies are presented. Long-term epidemiological interventions are addressed. Advocacy for smarter nickel use is reviewed. The American Academy of Pediatrics supports US legislation that advances safety standards (as modeled by the European Union) that protect children from early and prolonged skin exposure to high-nickel-releasing items. Our final aim for this article is to aid the pediatric community in developing nickel-avoidance strategies on both individual and global levels.

Genital vitiligo in children: Factors associated with generalized, non-segmental vitiligo.

BACKGROUND/OBJECTIVES: It remains uncertain as to whether genital vitiligo of childhood is segmental or a forme fruste of non-segmental disease. This type of vitiligo is sometimes termed figure-of-eight disease due to female predominance and perineal and perianal hypopigmentation or depigmentation around two orifices, the anal and vaginal introitus. The objective of this series was to categorize the features of genital-limited vitiligo of childhood including comorbidities, family history, and long-term course. METHODS: IRB-approved retrospective chart review of vitiligo cases. RESULTS: Eight cases of vitiligo that began in childhood in the genital area were identified, including clinical course and comorbidities. Involvement of the contiguous skin, including inner thighs, buttocks, and scrotum, was noted in all males. In females, only 1 patient had other sites of vitiligo, which was a solitary lesion on the chest. Therapeutic response to topical corticosteroids for perianal skin was seen in five of six children and topical calcineurin inhibitors with or without calcipotriene in four out of four patients. CONCLUSIONS: Segmental disease limited to the genitalia was more common in females than males, suggesting that perhaps intervention and work-up for comorbid autoimmune diseases may be required for males with genital-limited vitiligo at onset, but may be deferred in females and added if observation of spread is noted. Differentiation from lichen sclerosus et atrophicus may require biopsy.

Pediatric warts: update on interventions.

Warts are superficial viral infections of the skin that are extremely common in children. The infection usually lasts more than 1 year and can be moderately contagious in specific settings; for instance, warts are particularly common and spread more easily in the setting of atopic dermatitis, a chronic, itchy pediatric skin condition caused by barrier and immune defects. Therapies for pediatric warts are characterized according to 6 major categories: destructive; immune stimulating; immune modulating, including normalization of epithelial growth; vascular destructive; irritant; and nitric oxide releasing. The standard of care is the use of destructive therapies, with immune-stimulating and vascular destructive therapies reserved for more prolonged, extensive, or treatment-resistant infections. In this article, a successful paradigm for management of pediatric warts is provided, with enhanced outcomes based on further insight into the disease course and patient selection.

Skin diseases associated with atopic dermatitis.

Atopic dermatitis is a common chronic pruritic inflammatory skin disorder, characterized by an abnormal skin barrier, immune dysfunction, and an altered skin microbiome. Atopic dermatitis may be seen in conjunction with a variety of other skin disorders due to the complex pathogenesis of atopic dermatitis, involving genetic and environmental factors that are associated with immune dysfunction, barrier defects, and altered skin microbiomes. Skin disorders associated with atopic dermatitis include diseases sharing similar genetic origins like ichthyosis vulgaris, infectious diseases such as impetigo, and eczema herpeticum, in addition to the cutaneous autoimmune diseases, alopecia areata, and vitiligo. Atopic dermatitis is also often linked to such benign conditions as pityriasis alba and keratosis pilaris. This review discusses the cutaneous comorbidities of atopic dermatitis and their relationship via their occurrence in conjunction with atopic dermatitis.

Pediatric Stevens-Johnson syndrome and toxic epidermal necrolysis in the United States.

BACKGROUND: Little is known about the epidemiology of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in children. OBJECTIVE: We sought to determine the morbidity, mortality, and comorbid health conditions of SJS and TEN in US children. METHODS: This was a cross-sectional study of the 2009 to 2012 Nationwide Inpatient Sample, which contains a representative 20% sample of all US hospitalizations. Sociodemographics, inflation-adjusted cost, length of stay, comorbidities, and mortality were analyzed using descriptive statistics and multivariate regression analyses. RESULTS: The incidences of SJS, SJS-TEN, and TEN were a mean 5.3, 0.8, and 0.4 cases per million children per year in the US, respectively. Prolonged length of stay and higher costs of care (SJS: 9.4 ± 0.6 days, $24,947 ± $3171; SJS-TEN: 15.7 ± 1.5 days, $63,787 ± $8014; TEN: 20.4 ± 6.3 days, $102,243 ± $37,588) were observed compared with all other admissions (4.6 ± 0.1 days, $10,496 ± $424). Mortality was 0% for SJS, 4% for SJS-TEN, and 16% for TEN. In regression models, predictors of mortality included renal failure (adjusted OR [aOR] 300.28, 95% confidence interval [CI] 48.59->999.99), malignancy (aOR 54.33, 95% CI 9.40-314.22), septicemia (aOR 30.45, 95% CI 7.91-117.19), bacterial infection (aOR 20.38, 95% CI 5.44-76.36), and epilepsy (aOR 5.56, 95% CI 1.37-26.2). LIMITATIONS: Data regarding treatment were not available. Date of diagnosis of comorbidities was not present, precluding temporal analysis. CONCLUSIONS: Pediatric SJS/TEN poses a substantial health burden in the United States.

Pediatric periorificial dermatitis.

Periorificial dermatitis (POD) has been documented in the pediatric population in patients as young as 3 months, with a slight predominance in girls compared to boys. Many patients have a personal or family history of atopic disorders. Periorificial dermatitis typically presents with erythematous to flesh-colored papules and rarely pustules near the eyes, nose, and mouth. Although the etiology is unknown, many patients have had recent exposure to a topical or less commonly an inhaled or systemic corticosteroid. Although steroids may initially control the skin lesions, disease often rebounds after discontinuing therapy. Diagnosis of POD is clinical. Laboratory tests are not helpful in making the diagnosis, and the histology of POD resembles rosacea. It is important to rule out other acneform diagnoses based on the age of the patient, clinical history, and presentation of the lesions. Topical metronidazole has been successful in the pediatric population. For pediatric patients with extrafacial skin lesions or more severe disease, oral antibiotics such as tetracycline, doxycycline, minocycline, azithromycin, and erythromycin can be used, depending on the age of the patient.

Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants.

Vitiligo is an autoimmune disease in which depigmented skin results from the destruction of melanocytes, with epidemiological association with other autoimmune diseases. In previous linkage and genome-wide association studies (GWAS1 and GWAS2), we identified 27 vitiligo susceptibility loci in patients of European ancestry. We carried out a third GWAS (GWAS3) in European-ancestry subjects, with augmented GWAS1 and GWAS2 controls, genome-wide imputation, and meta-analysis of all three GWAS, followed by an independent replication. The combined analyses, with 4,680 cases and 39,586 controls, identified 23 new significantly associated loci and 7 suggestive loci. Most encode immune and apoptotic regulators, with some also associated with other autoimmune diseases, as well as several melanocyte regulators. Bioinformatic analyses indicate a predominance of causal regulatory variation, some of which corresponds to expression quantitative trait loci (eQTLs) at these loci. Together, the identified genes provide a framework for the genetic architecture and pathobiology of vitiligo, highlight relationships with other autoimmune diseases and melanoma, and offer potential targets for treatment.