Efficacy and safety of apremilast in pediatric patients with moderate-to-severe plaque psoriasis: 16-week results from SPROUT, a randomized controlled trial.

BACKGROUND: Approved systemic treatment options are limited for pediatric patients with moderate to severe plaque psoriasis. OBJECTIVE: To assess the efficacy and safety of apremilast over 16 weeks in pediatric patients with plaque psoriasis. METHODS: SPROUT (NCT03701763) was a phase 3, multicenter, randomized, double-blind, placebo-controlled study of apremilast in patients aged 6-17 years with moderate-to-severe psoriasis (Psoriasis Area and Severity Index [PASI] ≥12, body surface area ≥10%, static Physician Global Assessment [sPGA] ≥3) inadequately controlled by/inappropriate for topical therapy. Patients were stratified by age group and randomized (2:1) to apremilast (20 or 30 mg BID based on weight) or placebo for 16 weeks, followed by apremilast extension to 52 weeks. RESULTS: Of 245 patients randomized (apremilast: 163; placebo: 82), 221 (90%) completed the double-blind phase (apremilast: 149; placebo: 72). Significantly more patients achieved sPGA response and ≥75% reduction in PASI with apremilast than placebo, regardless of baseline age, weight, or disease severity. No new safety signals were observed. LIMITATIONS: Sample size of subgroup analyses. CONCLUSIONS: Improvements in global disease activity and skin involvement were significantly greater in pediatric patients treated with apremilast versus placebo. Adverse events were consistent with the known apremilast safety profile.

Arteriovenous malformation with hair collar sign.

We report the case of a newborn who was noted at birth to have an occipital scalp nodule presenting with a hair collar sign (HCS). The nodule had enlarged since birth. An MRI revealed a soft tissue mass on the occipital scalp without deep extension or cranial bone involvement. A biopsy of the nodule led to a diagnosis of arteriovenous malformation (AVM). A vascular malformation with HCS has not been reported before in North America. This case highlights the complexity of diagnosing a lesion with a hair collar sign.

Pediatric Dermatology in Canada: A Broad Review of Population Needs, Workforce and Training With Proposed Solutions.

INTRODUCTION: The need for pediatric dermatology services is increasing across Canada. In parallel, the complexity of treatment with novel targeted therapeutics has increased. Currently, there is no accredited and limited non-accredited fellowship training access to pediatric dermatology in Canada. HYPOTHESIS: Understanding the current state of pediatric dermatology training in Canada will provide insight into opportunities for strategic improvement. METHODS: A survey was distributed to 44 pediatric dermatology providers. In addition, a review of the burden of pediatric skin disease and education/training in Canada was performed. RESULTS: Thirty-four specialists responded to the survey (77% response rate). One third of current pediatric dermatology providers are over 50 years old and half of these (15%) plan to retire within the next 5 years. Half of respondents were dermatologists, 35% were pediatricians, and 11% were double boarded. Almost all respondents practiced in an academic setting (94%). Most had further fellowship training in pediatric dermatology (82.4%) but only 57% achieved this training in Canada, due to lack of accredited or non-accredited funded fellowship positions. CONCLUSION: There is a high and growing need for pediatric dermatology specialty care in a diverse range of settings. The current provider population and training programs are insufficient to meet current and future demands. We highlighted solutions to close this gap between supply and demand including increased double board certification in Pediatrics and Dermatology, a protected pediatric stream within existing Dermatology residency training programs and accredited fellowships in Pediatric Dermatology for both dermatologists and pediatricians.

Alopecia areata and subsequent Marie Antoinette syndrome following COVID-19 infection and vaccination: A case report.

Numerous cutaneous manifestations related to the COVID-19 (severe acute respiratory syndrome coronavirus 2) viral infection have been reported in literature. In this case report, we describe two acute hair-associated manifestations-the first being alopecia areata and the second is a case of Marie Antoinette syndrome or Canities subita where all the scalp hair has become white almost overnight. Both entities of hair changes were seen in the same patient.

Neonatal Curettage of Large to Giant Congenital Melanocytic Nevi Under Local Anesthetic: A Case Series With Long-Term Follow Up.

BACKGROUND: Neonatal curettage of large to giant congenital melanocytic nevi (L-GCMN) is a simple, minimally invasive procedure typically performed within the first 2 weeks of life. OBJECTIVES: To retrospectively review our experience with serial curettage of L-GCMN in the neonatal period performed under local anesthesia and their long-term outcomes. METHODS: Curettage was performed by a single pediatric dermatologist on nine neonates with L-GCMN under local anesthetic and with oral analgesia between 2002 and 2016 in Red Deer, Alberta, Canada. Patient charts were reviewed retrospectively to assess patient and procedure characteristics, tolerability, safety, cosmetic and functional outcomes, and malignant transformation. RESULTS: Patients were treated with an average of 6 curettage sessions (range 3 to 15) to remove the majority or entirety of the nevus. All patients tolerated local anesthesia well. The most common adverse event of the procedure was transient neutropenia. Two patients developed positive bacterial cultures without clinical signs of infection, treated with antibiotics. All curetted specimens demonstrated benign pathology. Patients were followed annually thereafter, for an average of 6 years. Eight patients with L-GCMN of the trunk had minimal to partial repigmentation with good cosmetic outcome. One patient had recurrence of a facial nevus. None of the patients developed cutaneous malignant melanoma. CONCLUSIONS: Curettage appears to be a safe and effective treatment option for select cases of L-GCMNs of the trunk. We do not recommend the procedure for face or scalp CMN. This procedure can be performed under local anesthesia with serial curettage to avoid potential risks of general anesthesia.

Systematic Review on the Efficacy and Safety of Oral Janus Kinase Inhibitors for the Treatment of Atopic Dermatitis.

Background: Atopic dermatitis is a chronic, relapsing and remitting disease that can be difficult to treat despite a recently approved biologic therapy targeting IL-4/IL-13 receptor. Oral janus kinase inhibitors (JAKi) represent a novel therapeutic class of targeted therapy to treat moderate-to-severe atopic dermatitis (AD). Objective: To review the efficacy, safety, and pharmacokinetic characteristics of oral JAKi in the treatment of AD. Methods: A PRISMA systematic review was conducted using MEDLINE, EMBASE (Ovid), and PubMed databases for studies assessing the efficacy, safety, and/or pharmacokinetic properties of oral forms of JAKi in the treatment of AD in pediatric or adult populations from inception to June 2021. Results: 496 papers were reviewed. Of 28 articles that underwent full text screening, 11 met our inclusion criteria for final qualitative review. Four studies examined abrocitinib; three studies examined baricitinib; three examined upadacitinib and one examined gusacitinib (ASN002). Significant clinical efficacy and a reassuring safety profile was reported for all JAKi agents reviewed. Rapid symptom control was reported for abrocitinib, baricitinib and upadacitinib. Limitations: Given the relatively limited evidence for each JAKi and the differences in patient eligibility criteria between studies, the data was not deemed suitable for a meta-analysis at this time. Conclusion: Given their ability to achieve rapid symptom control with a reassuring safety profile, we recommend considering the use of JAKi as a reliable systemic treatment option for adult patients with moderate-to-severe AD, who are unresponsive to topical or skin directed treatments.

Human Leukocyte Antigen Gene Testing and Carbamazepine-Induced Toxic Epidermal Necrolysis: A Study of Pediatric Practice.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening drug-induced dermatologic conditions. SJS/TEN occurs in 1-10 per 10 000 patients taking carbamazepine (CBZ) (Pratt VM, McLeod HL, Rubinstein WS et al. Medical Genetics Summaries. National Center for Biotechnology Information US; 2018: 1-527). The development of SJS/TEN is associated with variable drug metabolism and presence of an at-risk HLA haplotype. HLA-B*15:02 and HLA-A*31:01 haplotypes can produce a hyperimmune response in the setting of CBZ use in patients of Asian and European descent, respectively (Schneider JA, Cohen PR. Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A concise review with a comprehensive summary of therapeutic interventions emphasizing supportive measures. Adv Ther. 2017; 34:1235-1244). OBJECTIVE: The US Food and Drug Administration (FDA) and the Canadian pharmacogenomics Network for Drug Safety (CPNDS) recommend that patients with high-risk ethnic backgrounds should be genetic tested before initiating CBZ (Sukasem C, Chaichan C, Nakkrut T et al. Association between HLA-B Alleles and Carbamazepine-induced maculopapular exanthema and severe cutaneous reactions in Thai patients. Journal of Immunology Research. 2018; 1-11).We sought out to assess the awareness of this in prescribing practitioners and their standard of practice. METHODS: We created a 15-question survey and distributed to pediatric neurologists and pediatricians at the University of Alberta. We hypothesized that there was a discordance between the standard of practice and the recommendation by the FDA and CPNDS. RESULTS: The survey results indicated a lack of awareness of the at-risk ethnicities for CBZ-induced SJS/TEN. HLA gene testing was rarely done prior to initiation of CBZ in high-risk patients. In addition, there was a lack of awareness for standard of care for genetic testing in Canada and worldwide. CONCLUSIONS: Our results demonstrate an evident gap between current prescriber practices and existing FDA and CPNDS recommendations to screen for HLA genotypes. We hope that this study captures the realistic potential to improve patient outcomes.

A Clinicoepidemiological Study of Melanoma in Young Patients (20 Years of Age or Less) in Alberta, Canada, From 1992 to 2011.

The epidemiological trends of malignant melanoma have been well described in the literature. However, there remains a paucity of population-based studies assessing melanoma epidemiology in our younger patients (20 years of age or less). Other studies indicate that melanoma incidence has risen in pediatric populations over the last several decades and that these tumors may display different clinical characteristics from those arising in adult populations. We conducted a retrospective, population-based analysis of all incident cases of melanoma occurring in young patients aged ≤20 years in Alberta from 1992 to 2011. Information, including patient age, sex, anatomical location, date of diagnosis, histological subtype (if available), level of invasion, and date of death (if applicable), was obtained from the Alberta Cancer Registry. All cases occurring during a 10-year period from 1993 to 2011 have been reviewed. A total of 71 cases were diagnosed during this time (63% female and 37% male). Age range was 0-20 years (mean of 17.5 years). Truncal melanomas made up 36% of cases, while 28% occurred on the lower limbs, 17% on the upper limbs, and 18% in the head and neck region. Average Breslow thickness was 1.97 mm; 67% of tumors were less than 1 mm thick. Unfortunately, 8 of 71 patients died from their disease. Overall, the incidence of melanoma in patients aged ≤20 years appeared to decrease in Alberta in the past 20 years; however, there has been an increase in the thickness of melanoma at diagnosis, which needs to be addressed.

Cutaneous HPV16 and p16 Positive Basaloid Squamous Cell Carcinoma with Brain Metastasis: A Case Report.

Basaloid squamous cell carcinoma is an infiltrative and aggressive variant of squamous cell carcinoma with basaloid features. Primary skin-derived basaloid squamous cell carcinoma is rare. Basaloid squamous cell carcinoma is commonly observed in the oropharyngeal and anogenital regions and is associated with high-risk human papillomavirus. We report a case of primary basaloid squamous cell carcinoma overlying the right scapula with metastasis to the regional lymph nodes and brain despite surgical resection and adjuvant chemoradiation. Histopathologic investigations of high-risk cutaneous squamous cell carcinoma do not routinely involve human papillomavirus testing. In contrast, oncogenic human papillomavirus and p16 are screened in head and neck squamous cell carcinoma for prognostication. Since the patient presented with an aggressive variant of squamous cell carcinoma and distal metastasis despite standard therapies, human papillomavirus testing was performed. P16, a surrogate marker for human papillomavirus infection and specifically HPV16 was identified in the tumor. This is a unique report of HPV16 in primary cutaneous basaloid squamous cell carcinoma with distal brain metastasis.

Pharmacokinetics and safety of apremilast in pediatric patients with moderate to severe plaque psoriasis: Results from a phase 2 open-label study.

BACKGROUND: No oral systemic treatments are approved for pediatric patients with psoriasis. OBJECTIVE: To evaluate the pharmacokinetics and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in pediatric patients with psoriasis. METHODS: This phase 2, multicenter, open-label study enrolled pediatric patients with moderate to severe plaque psoriasis. Patients received apremilast twice daily without titration for 2 weeks (group 1 [age, 12-17 years; weight, ≥35 kg]: apremilast 20 or 30 mg; group 2 [age, 6-11 years; weight, ≥15 kg]: apremilast 20 mg), followed by a 48-week extension. Primary endpoints were pharmacokinetics and safety. Other endpoints were taste/acceptability and change from baseline in score on the Psoriasis Area and Severity Index. RESULTS: A total of 42 enrolled patients (21 adolescents [age, 12-17 years] and 21 children [age, 6-11 years]) received apremilast. Pharmacokinetics modeling and noncompartmental analyses showed that weight-based dosing with apremilast 20 mg twice daily in children or apremilast 20 or 30 mg twice daily in adolescents provides exposure (area under the concentration-time curve from time 0 to 12 hours after the dose) that is comparable to that achieved with apremilast 30 mg twice daily in adults. The safety profile was generally similar to that in adults. Most study participants liked the taste of the tablet. Improvements from baseline in mean Psoriasis Area and Severity Index score were 68% for adolescents (overall) and 79% for children. LIMITATIONS: No children weighing less than 20 kg were enrolled. CONCLUSIONS: This first-time-in-children phase 2 study supports weight-based apremilast dosing for future phase 3 studies of pediatric plaque psoriasis.

Management of pediatric plaque psoriasis using biologics.

BACKGROUND: Psoriasis is a chronic inflammatory disease with clinical manifestations of the skin that affect adults and children. In adults, biologics have revolutionized the treatment of moderate to severe plaque psoriasis where clear or almost clear is a tangible goal. Research on biologics has recently been extended to children. The introduction of these new therapeutic options has outpaced the limited guidelines in this population. OBJECTIVE: To provide a review of current data on biologics, with a proposal for a clinically relevant treatment algorithm on the management of moderate to severe plaque psoriasis in the pediatric population. METHODS: A Canadian panel with expertise in psoriasis, pediatric dermatology, and experience with consensus recommendation processes was selected to review the current landscape of pediatric psoriasis and clinical data on biologics plus identify special considerations for baseline workup and monitoring. Recommendations were reviewed and edited by each expert in an iterative process. CONCLUSION: A treatment algorithm for moderate to severe plaque psoriasis in pediatric patients is presented, incorporating approved biologics. Guidance on baseline screening and ongoing monitoring is also provided. Ultimately, treatment choice depends on the patient and his or her caregiver, with consideration of comorbidities, impact on quality of life, and relevant safety aspects.

Contemporary Role of Topical Calcineurin Inhibitors: A Pediatric Dermatology Perspective.

Atopic dermatitis (AD) is the most common pediatric chronic inflammatory skin disease in North America, often involving complex treatment regimens and impairing the quality of life of affected children and their families. Two topical calcineurin inhibitors (TCIs) have been available for the treatment of AD in pediatric patients for more than 15 years, and they continue to represent an important steroid-sparing option for the management of AD. Despite the large body of evidence and extensive clinical experience with these agents, there remain concerns among parents and clinicians regarding the long-term safety of this class of therapy, particularly with respect to the boxed warning about the potential risk of lymphoma and malignancy associated with TCIs. Concerns about burning or stinging with initial applications are also common. This review examines the literature on the clinical effectiveness of TCIs, with a focus on the pivotal research that supports the efficacy of these agents, and the reassuring body of evidence supporting their long-term safety in pediatric patients. Practical recommendations for maximizing the utility of TCIs in pediatric patients, including discussion points to address with parents, are offered.

Clinical Insights About Topical Treatment of Mild-to-Moderate Pediatric and Adult Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin condition, also referred to as atopic eczema, that is identified by itching and recurrent eczematous lesions. It often starts in infancy where it affects up to 20% of children but is also highly prevalent in adults. AD inflicts a significant psychosocial burden on patients and their families and increases the risk of other immune-mediated inflammatory conditions, such as asthma and allergic rhinitis, food allergy, and mental health disorders. It is a lifelong condition associated with epidermal barrier dysfunction and altered immune function. Through the use of emollients and anti-inflammatory agents, current prevention and treatment therapies attempt to restore epidermal barrier function. Acute flares are treated with topical corticosteroids. Topical calcineurin inhibitors (TCIs) and topical corticosteroids (TCSs) are used for proactive treatment to prevent remission. There remains a need and opportunity to improve AD care through future research directed toward an improved understanding of the heterogeneity of the disease and its subtypes, the role of autoimmunity in its pathogenesis, the mechanisms behind disease-associated itch and response to specific allergens, and the comparative effectiveness and safety of therapies.

Invasive melanoma in a 5-year-old Canadian patient: A case report.

Atypical Spitzoid lesions pose a distinct challenge in classification as they may comprise a mixture of both classic benign nevus and cutaneous melanoma characteristics. Immunostaining and molecular analysis, such as comparative genomic hybridization, can assist in narrowing the differential diagnosis. We present a case of a 5-year-old male with an atypical Spitzoid lesion on his back. Initial histopathology revealed a relatively symmetric lesion with mitotic figures and poor maturation of melanocytes with descent into the dermis. Immunohistochemistry demonstrated a loss of p16, and array comparative genomic hybridization revealed a loss of chromosome 9, supporting a diagnosis of invasive melanoma arising in conjunction with a remnant of a conventional melanocytic nevus. This case is the first in Canada to demonstrate the use of array comparative genomic hybridization for diagnosing melanoma in a young paediatric patient.

Topical sirolimus as an effective treatment for a deep neurofibroma in a patient with neurofibromatosis type I.

A 14-year-old boy with neurofibromatosis type I (NF1) presented with a painful neurofibroma on his right palm. The lesion was treated with topical sirolimus, resulting in decreased size and pain and improvement in motor function of his hand. This case demonstrates the efficacy of topical sirolimus in the management of neurofibromas in NF1.

Right Forearm Eruption Associated With Playing Minecraft: A Case of Contact Dermatitis Related to Computer Gaming.

This submission highlights the importance of careful history taking along with a strong index of suspicion for an exogenous cause of dermatitis. In particular, it highlights the importance of being aware of the latest trends and exposure risks for contact dermatitis.

Recurrent Pityriasis Rubra Pilaris: A Case Report.

Pityriasis rubra pilaris (PRP) is an uncommon papulosquamous dermatosis characterized by follicular, erythematous, hyperkeratotic papules coalescing to salmon-coloured plaques with islands of sparing. The disease tends to be self-limited and resolves spontaneously after a few years. In some cases, the disease is persistent. However, recurrence of this disease has rarely been described. An 8-year-old male was diagnosed with type III (classic juvenile) PRP. He was treated with acitretin, and his skin was clear after 6 months. He remained disease free for 6 years. At 14 years old, he was diagnosed again with type III PRP. His cutaneous manifestations were highly similar to his initial presentation. He was treated with acitretin and methotrexate concurrently and achieved skin clearance. Recurrence of type III PRP is possible although rarely described in the literature. Acitretin ± methotrexate therapy is effective at achieving skin clearance.

An Unanticipated Complication of Atopic Dermatitis.

An infant with a history of atopic dermatitis presented to the emergency department on 5 occasions with flulike symptoms. Eventually, this child presented with signs of infection and increased intracranial pressure: fever, bulging anterior fontanel, and leukocytosis. A computed tomography scan identified a large frontal lobe brain abscess. The abscess was surgically drained; culture was positive for Staphylococcus aureus. The initial source of the infected brain abscess was explored. Ultimately, it was thought to be secondary to impetiginized atopic dermatitis, an unusual but serious consequence of a common skin condition.

Disfiguring ulcerative neutrophilic dermatosis secondary to doxycycline and isotretinoin in an adolescent boy with acne conglobata.

Acne fulminans is an uncommon and debilitating disease that presents as an acute eruption of nodular and ulcerative acne lesions in association with systemic symptoms. It occurs commonly during treatment of severe acne (eg, acne conglobata) with isotretinoin in young adolescent male patients. Isotretinoin and doxycycline also can potentially induce development of neutrophilic dermatoses in patients with severe acne lesions, which are characterized by the acute appearance of painful ulcerative papulonodules accompanied by systemic symptoms including fever and leukocytosis. We report a challenging case of a 13-year-old adolescent boy who acutely developed hundreds of ulcerative plaques as well as systemic symptoms after being treated with doxycycline and isotretinoin for acne conglobata. He was treated with prednisone, dapsone, and colchicine and had to switch to cyclosporine to achieve relief from his condition.