The occurrence of mental health symptoms in isotretinoin-treated adolescents.

BACKGROUND: Isotretinoin treatment for acne can reduce adverse psychiatric outcomes in adults, but there has been little investigation of the incidence of psychiatric outcomes in treated adolescents. METHODS: This retrospective cohort study using the Rochester Epidemiology Project identified 606 patients aged 12-18 prescribed isotretinoin over a 10-year period between January 1, 2008 and December 31, 2017. Medical records were reviewed to identify psychiatric diagnoses before and during isotretinoin therapy, as well as psychiatric symptoms not captured by formal diagnoses and changes to isotretinoin dosing because of psychiatric diagnoses or symptoms. RESULTS: One hundred seventy-seven (29.2%) had a psychiatric diagnosis prior to isotretinoin initiation, but 98 (16.2%) had a new psychiatric diagnosis or psychiatric symptom while taking isotretinoin. Patients with a psychiatric history were no more likely than those without to receive a new psychiatric diagnosis during treatment (4.5% vs. 3.7%; p = .650), but did experience more psychiatric symptoms, primarily low mood and mood swings (23.7% vs. 7.7%; p < .001). Only 25.5% of the 98 with a new psychiatric diagnosis or psychiatric symptom had a subsequent dose change. A dose change was more likely if patients received a new psychiatric diagnosis (41.7% vs. 20.3%; p = .037) or patients did not have a psychosocial explanation for psychiatric symptoms (34.4% vs. 10.8%; p = .009). CONCLUSIONS: A substantial proportion of adolescent patients prescribed isotretinoin had a prior psychiatric diagnosis. This predicts more psychiatric symptoms during isotretinoin treatment. Adolescents with a psychiatric history who have worsening symptoms and those with new-onset psychiatric symptoms would benefit from close monitoring while taking isotretinoin.

Pathogenesis-directed treatment of linear porokeratosis with topical cholesterol-lovastatin.

A 2-year-old boy presented with an extensive, asymptomatic, photosensitive eruption refractory to topical steroids and tretinoin; examination and biopsies were consistent with generalized linear porokeratosis involving the face, limbs, and trunk. Treatment with topical cholesterol-lovastatin was initiated, and it successfully improved early erythematous lesions. Whole exome sequencing that targeted mevalonate pathway genes crucial in cholesterol synthesis later revealed a pathogenic, paternally inherited, porokeratosis-associated MVD, c.70+5 G>A, mutation. Topical cholesterol-lovastatin is a safe and effective empiric treatment for porokeratosis when used in the early, erythematous phase, and its success is likely mediated through its role in targeting mevalonate pathway mutations.

Pediatric Cutaneous Oncology: Genodermatoses and Cancer Syndromes.

Skin cancers represent the most common malignancy worldwide. In children, the diagnosis of skin cancer is rare and raises the possibility of an underlying genetic predisposition. Recent molecular advances have increased understanding of certain genetically determined regulatory pathways that constantly protect the skin from atypical cell growth and cancer. Knowledge about these underlying gene defects aids a dermatologist's ability to recommend confirmatory genetic testing and provides potential targets for future therapies. In this review, we outline genetic conditions important to dermatologists that are associated with skin cancer development and review the current approaches to the management of these patients.

An investigation of metabolic disturbances, including urinary stone disease, hypothyroidism, and osteoporosis in basal cell nevus syndrome.

BACKGROUND/OBJECTIVES: Basal cell nevus syndrome (BCNS) is an autosomal dominant skin cancer predisposition syndrome associated with abnormal mineral metabolism, a risk factor for urinary stone disease (USD). However, no research investigating the association between BCNS and USD or other manifestations of abnormal mineral metabolism has been conducted. The objective of this study is to investigate the association between BCNS and conditions associated with disordered mineral metabolism including USD, hypothyroidism, and osteoporosis and compare them to prevalence in the general population to elucidate potential unknown manifestations of the condition. METHODS: This retrospective study examined medical records of adult and pediatric patients with confirmed BCNS from the Mayo Clinic database from 1 January 1995 to 12 January 2020. Records were surveyed for evidence of USD and other comorbidities potentially related to BCNS. The studied cohort included 100 adult patients and 5 pediatric patients. RESULTS: A total of 105 patients were included in this analysis, 10 of whom experienced confirmed USD, representing a prevalence of 10%. Six adult patients were identified with a diagnosis of osteoporosis, representing a prevalence of 6%. Thirteen adult patients were identified with a diagnosis of hypothyroidism, representing a prevalence of 13%. CONCLUSIONS: This study identified a prevalence of USD in BCNS patients comparable to estimates of national prevalence, indicating that known abnormalities in mineral metabolism likely do not increase the incidence of USD in BCNS patients. Additional findings included increased prevalence of hypothyroidism and decreased prevalence of osteoporosis in the BCNS cohort compared to national averages.

Update on Clinically Relevant Genetic Testing in Pediatric Dermatology.

Clinical genetic testing enables the detection of specific gene mutations and variants that predispose individuals and their family members to disease. In recent years, tremendous strides have been made in the variety of clinically useful tests. Targeted testing for specific mutations that cause well-known syndromes enables the efficient diagnosis of genetic diseases with cutaneous manifestations. Testing for specific genes, however, may not always reveal a diagnosis. Expanded options are available. This review outlines the major types of available technology with a focus on those tests most useful for pediatric dermatologists.

Trends in utilization of non-first-line topical acne medications among children, adolescents, and adults in the United States, 2012-2016.

BACKGROUND/OBJECTIVE: Current knowledge about usage of effective, but non-first-line topical acne medications in the United States is limited. We aimed to investigate utilization patterns and temporal trends for such acne medications in the US ambulatory care. METHODS: Pediatric (≤18 years old) and adult (>18 years old) data from the 2012 to 2016 (inclusive) cycles of the US National Ambulatory Medical Care Survey were extracted. Utilization patterns of six non-first-line topical acne medications (ie, azelaic acid, salicylic acid, glycolic acid, sulfur, resorcinol, and zinc) were compared and followed over time. RESULTS: Data from 218 410 US office-based sampled visits during 2012-2016 were included in the analysis. Across all acne visits (n = 1542), salicylic acid (1.58%), azelaic acid (1.22%), and glycolic acid (0.52%) were the most frequently used agents, while zinc and resorcinol were not used. Sulfur (0.52%) and salicylic acid (0.33%) were the only medications used in preadolescents, and none of these medications were used in the neonatal or infantile group. Temporal trends for using at least one of these medications were insignificant among both pediatric and adult age groups (P = .825 and .136, respectively). CONCLUSIONS: Salicylic acid and azelaic acid are the most frequently used of the studied second-line medications to treat acne, although the use of these and the other non-first-line topical medications overall is uncommon, especially among younger groups of US pediatric patients.

Skin concerns in patients with trisomy 21 (Down syndrome): A Mayo Clinic 22-year retrospective review.

BACKGROUND/OBJECTIVES: Trisomy 21 has known associated clinical phenotypes, including skin and soft tissue concerns. However, the overall prevalence and types of findings are largely unclear. METHODS: A retrospective review of children with trisomy 21 and one or more dermatologic diagnoses, seen from 1/1/1994 to 7/1/2016, was performed to record dermatologic diagnoses. If one or more diagnoses were confirmed, further data were collected, including demographics, medical specialty, referrals to dermatology, treatment, complications, and follow-up. RESULTS: One hundred and seventy-four patients with a diagnosis of trisomy 21 aged 18 years or younger were confirmed to have one or more dermatologic diagnoses. In a total of 479 dermatologic diagnoses, superficial mycoses (12%), skin and soft tissue infections (10%), dermatitis (8%), and folliculitis (8%) were most common. Diagnoses were most commonly made as an outpatient (91%) and by general pediatrics (45%) or dermatology (25%). A significant difference (P < .05) in the frequency of various diagnoses made by different specialties was observed. A significant difference (P < .05) in the treatments recommended by different specialties was also observed. Referrals to dermatology were infrequent (6%). However, a frequent change in diagnosis (61%) or treatment (68%) for patients referred to dermatology was observed. CONCLUSIONS: Children with trisomy 21 are most commonly diagnosed with superficial mycoses, skin and soft tissue infections, dermatitis, and folliculitis. The majority of diagnoses were made by general pediatricians and although dermatology referral was rarely necessary, consultations often resulted in change of diagnosis and/or treatment, supporting consideration of early and frequent dermatology referral.

Parental neurotic excoriation injury of children: A case series of hidden physical abuse.

BACKGROUND: Recognizable skin findings of child physical abuse include bruises, abrasions, lacerations, bite marks, burns, and oral injuries. Self-induced skin picking, or neurotic excoriation, can correspond to emotional stress, underlying psychiatric illness, or substance abuse. Parental neurotic excoriation injury of children has not been reported previously as a form of physical abuse. METHODS: We present a case series of five children abused via parental excoriation. All affected children were three years of age or younger and otherwise healthy. Each child presented with wounds determined to be consistent with chronic picking. Patient age, injury location, and in some cases, witness accounts confirmed the lesions were not self-inflicted. RESULTS: In three cases, caregivers reported methamphetamine use. In these cases, caregivers repeatedly picked or wiped the infants' skin. In two cases, the caregiver demonstrated personal neurotic excoriation behavior, which was imposed upon her children resulting in similar lesions. One affected child died at 14 days of age from abusive head trauma, while the other four children were placed in foster care by Child Protective Services. CONCLUSION: Excoriation injury places children at risk for significant scarring and other long-term effects. We report examples demonstrating that repetitive skin injury by caregivers is a diagnostic consideration for abuse in young children.

Use of telemedicine for ichthyosis: Patient advocacy group as conduit to expert physician advice.

BACKGROUND/OBJECTIVES: Patients with rare diseases are challenged when it comes to finding physicians with expertise in their condition. The Foundation for Ichthyosis and Related Skin Types (FIRST) Tele-Ichthyosis program has provided telemedicine for patients and their families with keratinizing disorders since 2009. This study aims to characterize a decade of experience with the program. METHODS: This retrospective cohort study analyzed cases for demographics of patients and the clinicians who submitted their cases, nature of questions asked, number of expert responses, and characteristics of responses. Surveys were sent electronically to all users of the FIRST Tele-Ichthyosis service to assess experiences with the service and solicit constructive recommendations. Descriptive statistics were performed on the case review and responder surveys. RESULTS: Eighty-eight geographically diverse cases were reviewed showing increased use over time by various specialists for patients of all ages. Sixty-six percent of cases were definitively ichthyosis, and most submitters queried on diagnosis (47%) or treatment (72%). Most submitters described the service as easy to use (66.6%) and advice as timely (61.1%), clear (66.6%), and beneficial (61.1%). All submitters made suggestions for improvement (100%). Experts predominately worked with pediatric populations (70%) and reported self-motivation to volunteer and improve patients' lives (100%). Experts found technological barriers minor and provided feedback to enhance the service. CONCLUSIONS: This report highlights how a rare-disease patient advocacy group successfully supports physician collaboration and patient outcomes through secure and efficient telemedicine. Lessons learned are highly relevant in the current healthcare environment.

Use of spironolactone to treat acne in adolescent females.

BACKGROUND/OBJECTIVES: Studies assessing the utility of spironolactone for treating acne in adolescent females are lacking. Thus, we sought to examine spironolactone's role in treating this patient population. METHODS: A retrospective review was performed to determine the efficacy of spironolactone treatment in adolescent females seen at Mayo Clinic in Rochester, Minnesota, from 2007 to 2017. RESULTS: In a cohort of 80 pediatric patients with a median age of 19 years (range, 14-20 years), 64 patients (80%) experienced improvement of acne on treatment with spironolactone (median dose, 100 mg daily) with a favorable side effect profile. Approximately a quarter of patients (22.5%) had a complete response; more than half (58.8%) had a complete response or a partial response greater than 50%. Initial and maximal responses were observed at a median of 3 months and 5 months, respectively. Patients received treatment with spironolactone for a median duration of 7 months (range, 3-45 months) with limited side effects. CONCLUSIONS: Spironolactone demonstrated efficacy in treating acne in adolescent females and is a safe long-term alternative to systemic antibiotics in these patients.

The anatomic distribution of isolated and syndrome-associated port-wine stain.

BACKGROUND/OBJECTIVES: To determine the role of sex in port-wine stain (PWS) distribution and describe the epidemiologic and anatomic differences between syndrome-associated and non-syndrome-associated PWS using modern criteria. METHODS: A retrospective review of PWS patients aged 18 years and younger from 1995 to 2018 seen in the Department of Dermatology at an academic tertiary referral center. Cases were reviewed for sex, anatomic location, and presence of associated syndrome. 4,527 records were reviewed on the basis of ICD billing codes for congenital vascular malformations, with 516 meeting inclusion criteria. RESULTS: 516 patients were included in the analysis: 234 (45.4%) men and 282 (54.6%) women. A female preponderance of Sturge-Weber syndrome (18 of 23, 78%, P = .03) and a trend toward more female-isolated PWS (149 of 269, 55%, P = .72) were found. No lateral predominance observed for isolated PWS was found: 112(41.6%) limited left-side lesions and 113(42%) limited right-side lesions (P = .41). A trend toward Klippel-Trenaunay syndrome (KTS)-associated PWS occurring more commonly isolated to the left side (76 (45.5%) vs 59 (35.12%) P = .29) was found. Nine percent of SWS patients had a PWS on the body. Five percent of KTS patients had a facial PWS. The lower limb was the most common location overall of body PWS with 33.8% of isolated PWS and 81.5% of KTS patients having a lower limb lesion. CONCLUSIONS: Female children were more likely to be diagnosed with SWS, and a trend toward more isolated PWS in women was found. No lateral predominance of isolated PWS was found, but KTS-associated PWS was more common on the left. A considerable proportion of lesions do not appear in anatomic locations traditionally considered typical in the setting of associated syndromes, which underscores the importance of conducting a complete physical examination and adhering to diagnostic criteria for those syndromes.

Congenital ichthyosis in Prader-Willi syndrome associated with maternal chromosome 15 uniparental disomy: Case report and review of autosomal recessive conditions unmasked by UPD.

Prader-Willi syndrome (PWS) is a prototypic genetic condition related to imprinting. Causative mechanisms include paternal 15q11-q13 deletion, maternal chromosome 15 uniparental disomy (UPD15), Prader-Willi Syndrome/Angelman Syndrome (PWS/AS) critical region imprinting defects, and complex chromosomal rearrangements. Maternal UPD15-related PWS poses risks of concomitant autosomal recessive (AR) disorders when the mother carries a pathogenic variant in one of the genes on chromosome 15 associated with autosomal recessive inherited disease. Co-occurrence of autosomal recessive conditions in the setting of UPD leads to increased complexity of the clinical phenotype, and may delay the diagnosis of PWS. We report a patient with PWS and associated congenital ichthyosis due to maternal UPD15, and a homozygous novel pathogenic variant in ceramide synthase 3 (CERS3). We also review the literature of associated disorders reported in the setting of maternal UPD15-related PWS and provide a summary of the previously described CERS3 variants. This represents the second case of autosomal recessive congenital ichthyosis (ARCI) in the setting of PWS and UPD15. There needs to be a high index of suspicion of this genetic mechanism when there is unexpected phenotype or evolution of the clinical course in a patient with PWS.

Drug reaction with eosinophilia and systemic symptoms (DRESS) in the pediatric population: A systematic review of the literature.

BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a drug-induced hypersensitivity reaction that can have fatal complications. Although substantial data exist regarding DRESS in adults, to our knowledge, a systematic review of available literature has not been performed in children. OBJECTIVE: To review available data on DRESS in the pediatric population. METHODS: A systematic literature review was performed for pediatric (aged <18 years) patients with DRESS. RESULTS: We included 82 articles with 148 patients; of these, 97.9% experienced a skin rash, and the liver was the second most common organ involved (84.5%). Among 143 patients for which a treatment regimen was reported, 85.3% were treated with systemic steroids. Intravenous immunoglobulin alone failed to improve symptoms in 5 patients who were initially misdiagnosed, whereas those treated with intravenous immunoglobulin and steroids (2.7%) showed rapid clinical improvement. The mortality rate was low (3.0%). Complications included multiorgan failure and acute respiratory distress syndrome. LIMITATIONS: Limitations included limited availability of data for statistical analysis. CONCLUSION: Pediatric DRESS commonly involves the liver. With treatment, the prognosis is commonly good, but serious complications may occur. Corticosteroids, possibly in conjunction with intravenous immunoglobulin in severe cases, may serve as an effective, valuable treatment of pediatric DRESS.

Oral erosions associated with surreptitious marijuana vaping in an adolescent boy.

A 15-year-old boy presented with painful ulcerations affecting the oral mucosa that were eventually attributed to marijuana vaping. In this case report, we highlight cannabis vaping as a potential cause of oral erosions due to injury and chronic inflammation of the oral mucosa.

Fracture incidence in Ehlers-Danlos syndrome - A population-based case-control study.

BACKGROUND: The differential diagnosis of non-accidental injury during childhood includes medical conditions that predispose to skeletal fragility. Ehlers-Danlos syndrome (EDS) has been proposed as one such condition despite little objective evidence in the medical literature. OBJECTIVE: To investigate if EDS causes increased bone fragility during infancy and childhood. PARTICIPANTS AND SETTING: Residents of an 8-county region in southern Minnesota using the Rochester Epidemiology Project (REP) medical records-linkage system. METHODS: This retrospective, population-based, case-control study identified subjects with EDS from 1976 to 2015 who had complete records for at least their first year of life. Validity of diagnosis was ascertained using the 2017 International Classification of the Ehlers-Danlos Syndromes. Records were reviewed for fracture diagnoses that were characterized by age, location, type and mechanism. RESULTS: Of 219 potential cases, 21 had complete records for the first year of life and sufficient evidence in the medical record to support an EDS diagnosis. Of these 21, there were 14 hypermobile, 2 classical, 4 vascular, and 1 arthrochalasia EDS subtypes. 11 of 21 EDS cases (52.4%) and 15 of 63 controls (23.8%) had one or more fractures during childhood. No fractures were identified in the first year of life. Comparing cases to controls, EDS was associated with having any fractures during childhood with an odds ratio of 3.4 (95% CI: 1.20-9.66). CONCLUSIONS: We found no evidence that infants with common forms of EDS are predisposed to more frequent fractures. Ambulatory subjects with these EDS subtypes may have a higher incidence of fractures during childhood.

Temporal trends in prenatal risk factors for the development of infantile hemangiomas.

BACKGROUND/OBJECTIVES: Specific maternal risk factors have recently been identified in the development of infantile hemangiomas (IH), including gestational diabetes (GDM), maternal antihypertensive medication use or gestational hypertension (GHTN), maternal progesterone use, and artificial reproductive technologies (ART). We sought to explore the change in incidence of these risk factors over time and determine their association with the increased incidence of hemangiomas over 35 years, as previously reported. METHODS: The charts of 869 mother and infant pairs (infants previously diagnosed with IH between January 1, 1976, and December 31, 2010) were reviewed for prenatal complications. Rates of the prenatal complications over the 35-year period in birth mothers of infants diagnosed with IH were determined and evaluated by year of diagnosis (1976-1990, 1991-2000, and 2001-2010). RESULTS: Over the 35-year period in which the incidence of IH was previously examined, maternal age at delivery, prepregnancy body mass index (BMI), use of ART, maternal progesterone use, placental abnormalities, and GDM also increased. CONCLUSIONS: GDM, ART, and maternal progesterone use increased over the past 35 years, mirroring the previously reported trend of increasing incidence of IH. Maternal age and BMI also increased in mothers of infants with IH. Further exploration of this association may direct future research in the pathogenesis of infantile hemangiomas.